piperidines and Hypotension

The endocannabinoid system (ECS) is activated when natural arachidonic acid derivatives (endogenous cannabinoids or endocannabinoids) bind as lipophilic messengers to cannabinoid receptors CB1 and CB2. The ECS comprises many hydrolytic enzymes responsible for the endocannabinoids cleavage. These hydrolases, such as fatty acid amide hydrolase (FAAH) and monoacylglyceride lipase (MAGL), are possible therapeutic targets for the development of new drugs as indirect cannabinoid agonists. Recently, a new family of endocannabinoid modulators was discovered; the lead structure of this family is the nonapeptide hemopressin produced from enzymatic cleavage of the α-chain of hemoglobin and acting as negative allosteric modulator of CB1. Hemopressin shows several physiological effects, e.g., antinociception, hypophagy, and hypotension. However, it is still a matter of debate whether this peptide, isolated from the brain of rats, is a real neuromodulator of the ECS. Recent evidence indicates that hemopressin could be a by-product formed by chemical degradation of a longer peptide RVD-hemopressin during the extraction from the brain homolysate. Indeed, RVD-hemopressin is more active than hemopressin in certain biological tests and may bind to the same subsite as Rimonabant, which is an inverse agonist of CB1 and a μ-opioid receptor antagonist. These findings have stimulated several studies to verify this hypothesis and to evaluate possible therapeutic applications of hemopressin, its peptidic derivatives, and synthetic analogues, opening new perspectives to the development of novel cannabinoid drugs.

Topics: Analgesics; Animals; Cannabinoids; Endocannabinoids; Hemoglobins; Hypotension; Peptide Fragments; Piperidines; Protein Binding; Pyrazoles; Rats; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Opioid, mu; Rimonabant

Electrical cardioversion is an effective procedure for restoring normal sinus rhythm in the hearts of patients with irregular heart rhythms. It is important that the patient is not fully conscious during the procedure, as it can be painful and distressing. The drug used to make patients unaware of the procedure should rapidly achieve the desired level of sedation, should wear off quickly and should not cause cardiovascular or respiratory side effects.. We aimed to compare the safety, effectiveness and adverse events associated with various anaesthetic or sedative agents used in direct current cardioversion for cardiac arrhythmia in both elective and emergency settings.We sought answers to the following specific questions.• Which drugs deliver the best outcomes for patients undergoing electrical cardioversion?• Does using a particular agent confer advantages or disadvantages?• Is additional analgesic necessary to prevent pain?. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) on 27 March 2014. Our search terms were relevant to the review question and were not limited by outcomes. We also carried out searches of clinical trials registers and forward and backward citation tracking.. We considered all randomized controlled trials and quasi-randomized and cluster-randomized studies with adult participants undergoing electrical cardioversion procedures in the elective or emergency setting.. Two review authors independently assessed trial quality and extracted data, consulting with a third review author for disagreements. We used standard Cochrane methodological procedures, including assessment of risk of bias for all studies.. We included 23 studies with 1250 participants that compared one drug with one or more other drugs. Of these comparisons, 19 studies compared propofol with another drug. Seven of these compared propofol with etomidate (four of which combined the drugs with remifentanil or fentanyl), five midazolam, six thiopentone and two sevoflurane. Three studies compared etomidate with thiopentone, and three etomidate with midazolam. Two studies compared thiopentone with midazolam, one thiopentone with diazepam and one midazolam with diazepam. Drug doses and the time over which the drugs were given varied between studies. Although all studies were described as randomized, limited information was provided about the methods used for selection and group allocation. A high level of performance bias was observed across studies, as study authors had not attempted to blind the anaesthetist to group allocation. Similarly, study authors had rarely provided sufficient information on whether outcome assessors had been blinded.Included studies presented outcome data for hypotension, apnoea, participant recall, success of cardioversion, minor adverse events of nausea and vomiting, pain at injection site and myoclonus, additional analgesia and participant satisfaction. We did not pool the data from different studies in view of the multiple drug comparisons, differences in definitions and reporting of outcomes, variability of endpoints and high or unclear risk of bias across studies.. Few studies reported statistically significant results for our relevant outcomes, and most study authors concluded that both, or all, agents compared in individual studies were adequate for cardioversion procedures. It is our opinion that at present, there is no evidence to suggest that current anaesthetic practice for cardioversion should change.

Topics: Anesthetics; Apnea; Diazepam; Electric Countershock; Etomidate; Fentanyl; Humans; Hypnotics and Sedatives; Hypotension; Mental Recall; Methyl Ethers; Midazolam; Piperidines; Propofol; Randomized Controlled Trials as Topic; Remifentanil; Sevoflurane; Thiopental

Topics: Acidosis; Androstanes; Anesthesia; Anesthesia, General; Anesthesia, Inhalation; Anesthesia, Obstetrical; Anesthetics; Anti-Bacterial Agents; Anxiety; Contraceptives, Oral; Female; Ferricyanides; Fever; Humans; Hypnotics and Sedatives; Hypotension; Ketones; Male; Neuromuscular Nondepolarizing Agents; Occupational Diseases; Pain; Piperidines; Pregnancy; Pregnanes; Steroids; Tranquilizing Agents

Remimazolam confers a lower risk of hypotension than propofol. However, no studies have compared the efficacy of remimazolam and propofol administered using target-controlled infusion (TCI). This study aimed to investigate hemodynamic effects of remimazolam and target-controlled propofol in middle-aged and elderly patients during the induction of anesthesia.. Forty adults aged 45-80 years with the American Society of Anesthesiologists Physical Status 1-2 were randomly assigned to remimazolam or propofol group (n = 20 each). Patients received either remimazolam (12 mg/kg/h) or propofol (3 μg/mL, TCI), along with remifentanil for inducing anesthesia. We recorded the blood pressure, heart rate (HR), and estimated continuous cardiac output (esCCO) using the pulse wave transit time. The primary outcome was the maximum change in mean arterial pressure (MAP) after induction. Secondary outcomes included changes in HR, cardiac output (CO), and stroke volume (SV).. MAP decreased after induction of anesthesia in both groups, without significant differences between the groups (- 41.1 [16.4] mmHg and - 42.8 [10.8] mmHg in remimazolam and propofol groups, respectively; mean difference: 1.7 [95% confidence interval: - 8.2 to 4.9]; p = 0.613). Furthermore, HR, CO, and SV decreased after induction in both groups, without significant differences between the groups. Remimazolam group had significantly shorter time until loss of consciousness than propofol group (1.7 [0.7] min and 3.5 [1.7] min, respectively; p < 0.001). However, MAP, HR, CO, and SV were not significantly different between the groups despite adjusting time until loss of consciousness as a covariate. Seven (35%) and 11 (55%) patients in the remimazolam and propofol groups, respectively, experienced hypotension (MAP < 65 mmHg over 2.5 min), without significant differences between the groups (p = 0.341).. Hemodynamics were not significantly different between remimazolam and target-controlled propofol groups during induction of anesthesia. Thus, not only the choice but also the dose and usage of anesthetics are important for hemodynamic stability while inducing anesthesia. Clinicians should monitor hypotension while inducing anesthesia with remimazolam as well as propofol.. UMIN-CTR (UMIN000045612).

Topics: Adult; Aged; Anesthesia, General; Anesthetics, Intravenous; Hemodynamics; Humans; Hypotension; Middle Aged; Piperidines; Propofol; Unconsciousness

Rhinoplasty is a complex but popular surgery in Iran. The main complications of the surgery are post-operative bleeding and nasal septal hematoma due to poor intra-operative controlled hypertension. This study aimed to compare the efficacy of isoflurane-remifentanil (I-R) versus propofol-remifentanil (P-R) to induce controlled hypotension and to assess surgeon satisfaction with each of these combinations during rhinoplasty.. In 2020-2021, a single-blind clinical study was conducted on 98 patients aged 18-50 years undergoing rhinoplasty at Mother and Child Hospital (Shiraz, Iran). Patients were randomly divided into P-R (n=48) and I-R (n=50) groups. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were assessed during surgery and in the recovery room. A questionnaire was used to evaluate the level of surgeon satisfaction. Data were analyzed using independent samples. Five minutes after anesthesia induction, the P-R combination had a greater effect on reducing SBP (P=0.010), DBP (P=0.007), MAP (P=0.003), and HR (P=0.026) than I-R. However, from the 40. Both P-R and I-R combinations are recommended to induce hypotension during rhinoplasty. However, I-R is more effective than P-R in inducing the desired controlled hypotension.

Topics: Anesthetics, Intravenous; Child; Humans; Hypotension; Hypotension, Controlled; Isoflurane; Personal Satisfaction; Piperidines; Propofol; Remifentanil; Rhinoplasty; Single-Blind Method; Surgeons

Thoracic epidural analgesia (TEA) combined with general anesthesia decreases anesthetic requirements by half when hemodynamic criteria are used for the titration of analgesia. We therefore determined the impact of TEA on anesthetic requirements, when a closed-loop controller was used allowing the automated coadministration of propofol-remifentanil guided solely by the Bispectral index.. This single-center double-blind study enrolled patients scheduled for elective posterolateral thoracotomy using TEA. Patients were randomly assigned to receive a bolus followed by a continuous infusion of levobupivacaine 0.5% (levo group) or saline 0.9% solution (saline group). General anesthesia was performed by the same automated controller. Stroke volume optimization guided by an esophageal Doppler probe was performed before randomization. The primary outcome variable was the amount of remifentanil delivered by the automated controller between skin incision and closure. Major arterial hypotension was recorded. Data are presented as medians [interquartile range] or number (%) RESULTS:: Nineteen adult patients per group completed the study. At similar depth of anesthesia evaluated by the percentage of time with the Bispectral index in the range 40-60 (85 [77-88] vs 83 [72-87]; P = .39), patients with neuraxial block required less remifentanil (0.15 [0.10-0.20] vs 0.23 [0.14-0.25], µg·kg·min; P = .03) and propofol (4.3 [3.7-4.9] vs 5.7 [4.6-7.3] mg·kg·h; P = .005). Major arterial hypotension was similar in both groups (6 [32%] vs 5 [25%]; P = .46; levo versus saline group, respectively).. Epidurally administered levobupivacaine allowed a decrease by one-third of remifentanil requirement. After stroke volume optimization, major arterial hypotension was similar between groups.

Topics: Aged; Analgesia, Epidural; Anesthesia, Closed-Circuit; Anesthesia, Epidural; Anesthetics, Intravenous; Anesthetics, Local; Automation; Bupivacaine; Double-Blind Method; Elective Surgical Procedures; Female; Hemodynamics; Humans; Hypotension; Levobupivacaine; Male; Middle Aged; Piperidines; Propofol; Remifentanil; Thoracic Vertebrae; Thoracotomy; Thorax

Prewarming prior to surgery is effective in preventing perioperative hypothermia. There is a paucity of evidence, however, regarding the hemodynamic effects of prewarming. We hypothesized that the nadir mean arterial pressure during anesthesia induction would be higher after prewarming than after no prewarming.. We randomized 32 patients prior to elective neurosurgery to receive either one hour of forced-air convective warming at 46°C or routine care (full body blanket with convective warmer attached but not turned on). All patients had invasive blood pressure, heart rate, and core temperature monitoring before and during warming and underwent a protocolized intravenous anesthetic induction with propofol and remifentanil target-controlled infusions. The primary endpoint was the nadir mean arterial blood pressure (MAP) during induction. Hypotension was defined as systolic blood pressure (SBP) < 90 mmHg, MAP < 60 mmHg, or a reduction in either SBP or MAP > 20% from baseline values.. No difference was found in the mean (SD) nadir MAP between the prewarmed group and the control group [64 (11) mmHg vs 68 (16) mmHg, respectively; mean difference, 5 mmHg; 95% confidence interval (CI), -6 to 15; P = 0.36]. Similarly, there was no difference between groups in the incidence of hypotension (100% of prewarmed vs 93% of control patients; relative risk, 1.07; 95% CI, 0.94 to 1.23; P = 0.32) or in the requirement for vasopressors during induction (four patients in each group required metaraminol; P = 1.00).. Prewarming with convective forced air for one hour prior to intravenous anesthetic induction did not prevent hypotension during the induction period (Australian New Zealand Clinical Trials Registry [ANZCTR] ACTRN12615000431527).

Topics: Adult; Aged; Anesthetics, Intravenous; Blood Pressure; Body Temperature; Female; Heart Rate; Humans; Hypotension; Hypothermia; Incidence; Male; Metaraminol; Middle Aged; Neurosurgical Procedures; Piperidines; Propofol; Remifentanil

We aimed to compare fentanyl, remifentanil and dexmedetomidine with respect to hemodynamic stability, postoperative pain control and achievement of sedation at the postanesthetic care unit (PACU). In this randomized double-blind study, 90 consecutive total laparoscopic hysterectomy patients scheduled for elective surgery were randomly assigned to receive fentanyl (1.0 μg/kg) over 1 minute followed by a 0.4 μg/kg/hr infusion (FK group, n = 30), or remifentanil (1.0 μg/kg) over 1 minute followed by a 0.08 μg/kg/min infusion (RK group, n = 30), or dexmedetomidine (1 μg/kg) over 10 minutes followed by a 0.5 μg/kg/hr infusion (DK group, n = 30) initiating at the end of main procedures of the operation to the time in the PACU. A single dose of intravenous ketorolac (30 mg) was given to all patients at the end of surgery. We respectively evaluated the pain VAS scores, the modified OAA/S scores, the BIS, the vital signs and the perioperative side effects to compare the efficacy of fentanyl, remifentanil and dexmedetomidine. Compared with other groups, the modified OAA/S scores were significantly lower in DK group at 0, 5 and 10 minutes after arrival at the PACU (P < 0.05), whereas the pain VAS and BIS were not significantly different from other groups. The blood pressure and heart rate in the DK group were significantly lower than those of other groups at the PACU (P < 0.05). DK group, at sedative doses, had the better postoperative hemodynamic stability than RK group or FK group and demonstrated a similar effect of pain control as RK group and FK group with patient awareness during sedation in the PACU. (World Health Organization registry, KCT0001524).

Topics: Adolescent; Adult; Analgesics, Opioid; Blood Pressure; Dexmedetomidine; Double-Blind Method; Female; Fentanyl; Heart Rate; Hemodynamics; Humans; Hypotension; Laparoscopy; Male; Middle Aged; Nausea; Pain Management; Pain, Postoperative; Piperidines; Remifentanil; Young Adult

Current guidelines recommend monitoring the anesthetic depth of sedation during respiratory endoscopy by using clinical scales despite their subjective nature and the potential change in the level of sedation caused by frequent stimulation. Monitoring by means of the bispectral index (BIS) has shown its utility in reducing the use of drugs and their adverse events in general anesthesia, but evidence in prolonged sedation is insufficient.. Our objective was to evaluate BIS in patients undergoing endobronchial ultrasound (EBUS).. A randomized cohort study of 90 patients with mediastinal lymph node involvement and/or lung or mediastinal lesions for whom EBUS was indicated, comparing the modified observer's assessment of alertness/sedation scale clinical evaluation (n = 45) versus the BIS evaluation (n = 45) of sedation with propofol-remifentanil, was conducted in order to evaluate the clinical parameters, doses used, adverse events, and tolerance of the procedure.. We found a shorter waking time and a significantly lower dose of total propofol in the BIS group. Significantly fewer overall adverse events were recorded in the BIS group and included desaturation, hypotension, and bradypnea. Tolerance was better in the BIS group. No significant differences were found in terms of cough, memory of the procedure, or the level of difficulty of EBUS on the part of the pulmonologists.. BIS monitoring of sedation in EBUS makes it possible to reduce the dosage of propofol, thereby shortening the waking time and reducing adverse events. This form of monitoring should be taken into consideration in the future for systematic use in prolonged sedation, as in the case of EBUS.

Topics: Aged; Anesthetics, Intravenous; Bronchoscopy; Consciousness Monitors; Deep Sedation; Endosonography; Female; Humans; Hypotension; Intraoperative Complications; Lymph Nodes; Male; Mediastinum; Middle Aged; Monitoring, Intraoperative; Piperidines; Propofol; Remifentanil

Extracorporeal Shock Wave Lithotripsy is usually performed in day surgery setting, consequently people who undergo to this procedure need a safe and fast recovery. Conscious sedation with remifentanil can relieve from pain and keep patients in touch with anaesthesiologists. Few publications tell about infusion rates administered to perform this procedure7. The aim of this study is to assess which is the most appropriate infusion rate.. Patients were randomly assigned to two groups. Two different infusion rates were compared: 0,05 mcg/kg/min, GROUP A (N.=114), vs. 0.1 µg/kg/min, GROUP B (N.=114). Patients' vital signs, additional analgesic requests, PONV (postoperative nausea and vomiting) and other side effects were registered. The deepness of sedation and patient's satisfaction were evaluated referring to Obsever's Assessment of Alertness and Sedation scale (O/ASS) and using a Likert's scale respectively. Pain intensity was assessed with a 11-points VAS (visual analogue scale). Differences between groups were analyzed using Student t test for independent variables. The χ2 test was used to analyze categorical variables.. The study enrolled 228 patients and assigned them to two groups (N.=114). No significant differences were found regarding Likert's scale values (P=0.20), additional analgesic request (P=0.30) and mean VAS values (P>0.05) between the two groups. The difference between the two groups about PONV, hypotension, oxygen desaturation and respiratory depression was statistically significant (P<0.05), as a matter of fact in group A these side effects occurred less frequently. The fifth degree of O/ASS was estimated in about 1.61±0.19 min and 2.987±0.20 min in group A and in group B respectively (P<0.05).. According with previous results remifentanil at the infusion rate of 0.05 µg/kg/min provides an effective analgesia, causing a lower incidence of side effect than 0.1 µg/kg/min, granting a fast and safe recovery.

Topics: Analgesia; Anesthesia, Intravenous; Anesthetics, Intravenous; Conscious Sedation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hemodynamics; Humans; Hypotension; Hypoxia; Incidence; Infusions, Intravenous; Lithotripsy; Male; Middle Aged; Pain, Postoperative; Patient Satisfaction; Piperidines; Postoperative Complications; Postoperative Nausea and Vomiting; Remifentanil; Urolithiasis

Maintaining blood pressure (BP) and heart rate (HR) after laryngoscopy and tracheal intubation has always been a concern in injured patients. Opioids can attenuate or stop an increase in these two parameters if administered with proper doses or targets in target-controlled infusion (TCI). Remifentanil and sufentanil are widely used for this purpose because their cardiac side effects are low and, especially in traumatic patients, they are tolerated well. A comparison of the benefits and limitations of these two opioids in TCI is much needed. A literature review in electronic data bases revealed few results.. 40 normotensive patients were enrolled to this randomized clinical trial study. After BIS guided anesthesia with a target-controlled propofol infusion and muscle relaxation with cisatracurium, remifentanil and sufentanil were infused using TCI with 2 and 0.2 ng.ml-1 targets respectively. BP and HR were recorded for five data points and compared with Fischer's exact test.. Systolic, mean and diastolic arterial pressure and HR in different points of the study remained below baseline values but were out of control in some cases, however the out-of-control values showed significant difference between the two groups only for heart rate changes. The relative risk for producing out-of-control changes with remifentanil compared to sufentanil is significantly more than 1 for HR decrease.. Sufentanil produced more common pre-intubation hypotension than remifentanil in propofol anesthetized patients but this hypotension disappeared sooner than remifentanil after tracheal intubation. Both opioids prevent an increase in BP and HR after tracheal intubation but the side effects (hypotension and bradycardia) may be a cause for concern (IRCT138710011361N3).

Topics: Adult; Anesthesia; Anesthetics, Intravenous; Blood Pressure; Bradycardia; Dose-Response Relationship, Drug; Drug Monitoring; Female; Heart Rate; Humans; Hypotension; Intraoperative Complications; Intubation, Intratracheal; Male; Middle Aged; Outcome Assessment, Health Care; Piperidines; Remifentanil; Sufentanil; Wounds and Injuries

Mesenteric traction syndrome (MTS) is caused by PGI(2) release during abdominal procedures and is often observed during abdominal surgery. We have demonstrated that MTS occurs more frequently in cases using remifentanil than in those that are not. The aim of this study was to assess the prophylactic benefit of flurbiprofen axetil on MTS in patients undergoing abdominal surgery using remifentanil.. Thirty ASA physical status I and II patients were enrolled. They were scheduled to undergo abdominal surgery under general anesthesia with remifentanil and were randomly assigned to receive flurbiprofen axetil (group F) or saline (group C) preoperatively (n = 15 each). MTS was defined according to our simplified diagnostic criteria. Arterial blood pressure and heart rate were recorded, and the plasma 6-keto-PGF(1α) (a stable metabolite of PGI(2)) concentration was measured just before skin incision and at 20 and 60 min after skin incision (T(0), T(20), T(60)) to confirm the diagnosis of MTS.. Twelve of 15 (80%) patients developed MTS in group C, whereas only 1 of 15 (6.7%) patients in group F developed MTS. At T(20), the group C patients showed significantly lower arterial blood pressure (P < 0.05) and a faster heart rate (P < 0.01) than those in group F. The mean plasma 6-keto-PGF(1α) concentration was significantly elevated in group C at T(20) (P < 0.01), whereas the plasma 6-keto-PGF(1α) level remained low throughout the observation period in group F.. We found that preoperative administration of flurbiprofen axetil reduced the incidence of MTS during abdominal surgery with remifentanil analgesia.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Aged; Anesthesia, General; Anesthetics, Intravenous; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Epoprostenol; Female; Flurbiprofen; Humans; Hypnotics and Sedatives; Hypotension; Infusions, Intravenous; Laparotomy; Male; Midazolam; Middle Aged; Piperidines; Postoperative Complications; Preanesthetic Medication; Prospective Studies; Remifentanil; Splanchnic Circulation

Donepezil is a widely used cholinesterase inhibitor for the treatment of Alzheimer's disease (AD), however its cholinergic adverse side effects on the cardiovascular system are still unclear. In this study, we aimed to examine the adverse side effects caused by donepezil on cardiac rhythm and postural blood pressure changes in elderly patients with Alzheimer Disease.. The ECG parameters including heart rate, PR, QT, QTc interval and QRS duration and postural blood pressure changes were recorded at the baseline and at each donepezil dose level (5 and 10 mg/d). Patients Seventy-one consecutive patients who were referred by primary care centers to a Geriatric Clinic were enrolled and underwent comprehensive geriatric assessment.. Fifty-two subjects completed the study. There were no significant changes relative to the baseline in any of the ECG parameters or arterial blood pressure at any of the investigated dosages of donepezil.. It was demonstrated that donepezil was not associated with increased negative chronotropic, arrhythmogenic or hypotensive effects for elderly patients with Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Arrhythmias, Cardiac; Blood Pressure; Cholinesterase Inhibitors; Donepezil; Electrocardiography; Female; Gastrointestinal Diseases; Heart Rate; Humans; Hypotension; Indans; Male; Nootropic Agents; Piperidines

The increased distribution of crystalloid solution into the interstitial space may decrease the effectiveness of intravascular volume loading in patients. We investigated whether preoperative hydration status after overnight fasting affects interstitial fluid redistribution and thus the magnitude of hypotension during general anesthesia.. Sixty ASA physical status I/II patients undergoing tympanoplasty fasted from midnight. Anesthesia was induced by fentanyl and propofol and maintained with sevoflurane and remifentanil. Coinciding with the induction of anesthesia, 15 mL/kg acetated Ringer solution was infused IV over 60 minutes followed by 1 mL/kg acetated Ringer solution over the next 30 minutes. Urine osmolalities after induction of anesthesia and during the study period (pre-U(osm), post-U(osm)) and percent decreases of whole-body bioelectrical resistance for extracellular fluid relative to baseline at the end of the study period (ΔR(e)) were measured. Patients with a pre-U(osm) < the 25th percentile or with a pre-U(osm) > the 75th percentile of pre-U(osm) were categorized in the hydrated or the dehydrated group, respectively. A range of variables, including mean arterial blood pressure during the 30- to 90-minute period relative to baseline, and ΔR(e), were compared between the groups.. The dehydrated group (pre-U(osm) >759.5 mOsm/kg, n = 15) had a lower age (44 vs 52 years, P = 0.049) and had a higher post-U(osm) (181 vs 55 mOsm/kg, P = 0.001) compared with the hydrated group (pre-U(osm) <378.5 mOsm/kg, n = 15). Mean arterial blood pressure during the 30- to 90-minute period relative to baseline (0.67 vs 0.67, P = 0.85) with 95% confidence interval for the difference of means (-0.070 to 0.084) and ΔR(e) (5.6% vs 6.0%, P = 0.58) with 95% confidence interval for the difference of means (-1.85% to 1.06%) were similar for the hydrated and dehydrated groups.. Preoperative dehydration after overnight fasting as measured by urine osmolality did not alter the magnitude of hypotension during general anesthesia. This finding suggests that intravascular volume loading with crystalloid solution to prevent hypotension during general anesthesia is an unfounded practice for low risk patients after overnight fasting.

Topics: Adult; Anesthesia, General; Blood Pressure; Crystallization; Electric Impedance; Female; Fentanyl; Humans; Hypotension; Male; Methyl Ethers; Middle Aged; Osmolar Concentration; Piperidines; Propofol; Remifentanil; Risk; Sevoflurane; Time Factors; Treatment Outcome; Tympanoplasty; Urine

This study was conducted to examine whether pretreatment with intravenous atropine could prevent bradycardia and hypotension during induction of total intravenous anesthesia with propofol and remifentanil in a prospective randomized placebo-controlled manner. Seventy patients, aged 24-78 years, were randomly divided into two groups, and received 0.5 mg atropine or placebo saline 1 min before induction of intravenous anesthesia with remifentanil at 0.4 microg/kg/min, propofol at a target blood concentration of 3 microg/ml, and vecuronium 1.5 mg/kg. Immediately after tracheal intubation, the infusion rate of remfentanil and the target concentration of propofol were reduced to and kept at 0.1 microg/kg/min and 2 microg/ml, respectively, for 10 min. Noninvasive blood pressure (BP) and heartrate (HR) were measured and recorded every minute. Intravenous atropine could prevent a fall in HR, but not a fall in BP, during induction of intravenous anesthesia with propofol and remifentanil of our dosing regimen. Our data suggested that a fall in HR induced by propofol-remifentanil anesthesia was mainly caused by centrally mediated sympatholytic and/or vagotonic actions of propofol and remifentanil, whereas a fall in BP was mainly the result of their direct vasodilating actions.

Topics: Adult; Aged; Anesthesia, Intravenous; Anesthetics, Intravenous; Atropine; Bradycardia; Female; Humans; Hypotension; Male; Middle Aged; Parasympatholytics; Piperidines; Propofol; Prospective Studies; Remifentanil; Treatment Outcome; Young Adult

The use of remifentanil is often associated with the observation of mesenteric traction syndrome (MTS) soon after manipulation of the intestine during abdominal surgery. MTS symptoms include facial flushing, hypotension, and tachycardia. In the study reported here, we prospectively investigated the effects of remifentanil on the incidence of MTS in abdominal surgery.. One hundred patients scheduled for abdominal surgery were randomly assigned to two groups. In one group (n = 50), fentanyl alone was used as intravenous analgesic (control, group C); in the second group (n = 50), both fentanyl and remifentanil were used (remifentanil group, group R). In all patients, anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane inhalation. Remifentanil was continuously infused for patients in group R as an analgesic. Plasma concentration of 6-keto-PGF(1α) was measured before surgery and 20 min after the skin incision was made in six patients of group R and seven patients of group C.. MTS occurred in 20 cases in group R (40.0%), but in only five cases in group C (10.0%). In both groups, the incidence of MTS was higher in laparotomy than in laparoscopic surgery. The plasma concentration of 6-keto-PGF(1α) was low in both groups before surgery and was elevated 20 min after skin incision in both groups in patients in whom MTS appeared.. The results of this study suggest that the use of remifentanil in laparotomy facilitates MTS.

Topics: 6-Ketoprostaglandin F1 alpha; Abdomen; Aged; Anesthesia Recovery Period; Anesthesia, General; Anesthetics, Intravenous; Flushing; Hemodynamics; Humans; Hypotension; Intraoperative Complications; Laparotomy; Mesentery; Middle Aged; Piperidines; Prospective Studies; Remifentanil; Splanchnic Circulation; Syndrome; Tachycardia

Emergence from general anesthesia can be associated with coughing, agitation, and hemodynamic disturbances. Remifentanil may attenuate these responses.. In a prospective, double-blind, randomized trial, we enrolled 60 adult patients undergoing nasal surgery using remifentanil-based anesthesia. During the emergence phase, the remifentanil group had remifentanil reduced to one tenth of the maintenance rate, whereas the control group had remifentanil discontinued.. Times to awakening and tracheal extubation were similar between the two groups. During emergence, the remifentanil group (infusion rate 0.014 +/- 0.011 microg x kg(-1) x min(-1)) had a significantly lower incidence (40% vs 80%, P = 0.002) and less severe coughing compared with the control group, as well as a lower incidence of nonpurposeful movement (3.3% vs 30%, P = 0.006) and slower heart rates.. Low-dose remifentanil during emergence did not prolong wake-up but reduced the incidence and severity of coughing from the endotracheal tube.

Topics: Adolescent; Adult; Analgesics, Opioid; Anesthesia Recovery Period; Anesthesia, General; Blood Pressure; Cough; Double-Blind Method; Drug Administration Schedule; Female; Heart Rate; Humans; Hypotension; Infusions, Intravenous; Intubation, Intratracheal; Male; Middle Aged; Nose; Piperidines; Prospective Studies; Psychomotor Agitation; Remifentanil; Severity of Illness Index; Tachycardia; Time Factors; Treatment Outcome; Young Adult

To assess the effect of esmolol added to propofol-remifentanil combination for hypotensive anesthesia on hemodynamic conditions, consumption of anesthetic drugs, and recovery, during elective septorhinoplasty.. This prospective, randomized study was carried out at Gazi University, Faculty of Medicine, Ankara, Turkey in 2005. Following Institutional Ethical Committee approval, 40 American Society of Anesthesiologists (ASA) I patients were divided into 2 equal groups group remifentanil infusion RP and group esmolol infusion (RP-E). After anesthesia induction with propofol (2-2.5 mg/kg), the mean arterial pressure was aimed to be between 50 mm Hg and 65 mm Hg for controlled hypotensive anesthesia in both groups. In group RP, a remifentanil infusion of 0.1-0.5 microg/kg/min was titrated, following a bolus of 1 microg/kg; for group RP-E, an esmolol infusion of 100-300 mg/kg/min was titrated, following a bolus of 500 microg/kg; to achieve a target blood pressure. In addition, propofol was infused according to depth of anesthesia to maintain anesthesia in both groups. Electrocardiography, heart rate, blood pressure, cardiac output, and consumption of anesthetic drugs were recorded. Postoperatively, recovery times, visual analog pain scores, and side effects were observed.. The decrease in the intraoperative heart rate was more significant in group RP-E than in group RP. The remifentanil consumption was much lower in group RP-E. The recovery times were similar in both groups.. Addition of esmolol to propofol-remifentanil combination leads to a decrease in remifentanil consumption, without a decrease in cardiac output during hypotensive anesthesia.

Topics: Adolescent; Adult; Anesthetics; Hemodynamics; Humans; Hypotension; Middle Aged; Piperidines; Propanolamines; Propofol; Remifentanil; Young Adult

In neuroanesthesia practice, muscle relaxants may at times need to be avoided to facilitate intraoperative motor pathway monitoring. Our study's objective was to determine the optimal dose of remifentanil required to prevent movement after neurosurgical stimulation.. After Institutional Review Board approval and written informed consent, 132 patients undergoing elective craniotomy randomly received one of 12 remifentanil dose regimens (0.10 to 0.21 microg/kg/min). Remifentanil was started before induction with propofol and succinylcholine. Anesthesia was maintained with isoflurane (0.6% end-tidal) in air/oxygen. During the study, movement was assessed on predetermined criteria by the anesthesiology, nursing, and neurosurgical teams. Heart rate and blood pressure were recorded every 5 minutes. We assessed the relationship between movement, hypotension, bradycardia, and dose using probit analysis and logistic regression.. Sixty-five percent of the patients moved in response to surgical stimuli [95% confidence interval (CI): 49%-79%] at a remifentanil infusion rate of 0.10 microg/kg/min, and movement decreased to 21% (95% CI: 11-35) at 0.21 microg/kg/min. The probability of movement was 50% at an infusion rate (95% CI) of 0.13 (0.10 to 0.15) microg/kg/min remifentanil and decreased to 25% at an infusion rate of 0.19 (0.17 to 0.29) microg/kg/min. The probability of hypotension and bradycardia was 50% at 0.13 (0.10 to 0.15) microg/kg/min and 0.17 (0.15 to 0.21) microg/kg/min, respectively.. Higher doses of remifentanil lessen the risk of movement in the absence of muscle relaxants with surgical stimulation for elective craniotomy. Hypotension and bradycardia were common at higher doses. Even at the maximum dose (0.21 mcg/kg/min) there was a 20% chance of movement. Adjunctive therapy is needed to ablate movement reliably, and to counteract the hypotensive effect of remifentanil. These findings may be helpful for clinicians administering remifentanil and isoflurane during procedures, where muscle relaxants may not be desirable.

Topics: Adult; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Blood Pressure; Bradycardia; Brain Neoplasms; Craniotomy; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heart Rate; Humans; Hypotension; Intraoperative Complications; Intraoperative Period; Intubation, Intratracheal; Isoflurane; Male; Middle Aged; Movement; Neuromuscular Blockade; Neurosurgical Procedures; Piperidines; Prospective Studies; Remifentanil

We evaluated the use of continuous infusion of ketamine to reduce intraoperative remifentanil side effects, such as bradycardia and hypotension, and to improve postoperative analgesia from balanced anesthesia with remifentanil.. Forty patients undergoing spine surgery under remifentanil-based anesthesia were randomly assigned to intraoperative ketamine group and saline (control) group. Balanced anesthesia was maintained with infusion of propofol (2-4 mg x kg(-1) x hr(-1)), remifentanil (6-8 microg x kg(-1) hr(-1)) and vecuronium (60-80 microg x kg(-1) x hr(-1)) with nitrous oxide (60%) and with or without ketamine (300-400 microg x kg(-1) x hr(-)). All patients were given scheduled NSAIDs by their own doctor at the end of surgery. Intraoperative bradycardia (HR <50) and hypotension (SBP <80), and postoperative additional NSAIDs request were recorded.. Adverse events, such as bradycardia and hypotension, were less frequent in the ketamine group (P < 0.05). Less additional NSAIDs was required in the ketamine than in the control group (P < 0.05). Emergence time from anesthesia was within 5 min in both groups.. Remifentanil-based anesthesia with continuous ketamine decreases intraoperative side effects and postoperative NSAIDs request. Thus, intraoperative continuous ketamine may be a useful adjuvant to remifentanil.

Topics: Adjuvants, Anesthesia; Adult; Anesthesia, General; Anti-Inflammatory Agents, Non-Steroidal; Bradycardia; Humans; Hypotension; Infusions, Intravenous; Intraoperative Complications; Ketamine; Middle Aged; Pain, Postoperative; Piperidines; Remifentanil; Spine

Propofol produces anaesthesia with rapid recovery but also causes pain or discomfort on injection. The effect of remifentanil in prevention of propofol-induced injection pain has been demonstrated in earlier studies. However, sufentanil, an opioid analgesic, has not been evaluated as an agent for managing pain on injection of propofol. In this study we aimed to compare the efficacy of remifentanil and sufentanil for the prevention of propofol-induced pain.. This double-blind, placebo-controlled clinical study was carried out from July 2006 to February 2007, and included patients who were candidates for elective surgery in a university hospital. From 92 American Society of Anesthesiologists (ASA) status I-II adult patients, 80 were randomly assigned to four groups of 20 each. Patients received 2 mL of sufentanil 0.01 mg, 2 mL of remifentanil 0.01 mg, 2 mL of remifentanil 0.02 mg, or 2 mL of saline 60 seconds prior to administration of 5 mL of propofol 1%. Patients were asked prior to losing consciousness whether they felt any pain due to propofol injection, and their pain scores were evaluated on the four-point scale of Ambesh et al.. The incidence of pain was significantly lower in the remifentanil 0.02-mg group, remifentanil 0.01-mg group and sufentanil group compared with the saline group (40%, 70%, 75% and 100%, respectively, p < 0.05). Median pain intensity scores were significantly lower in the group receiving remifentanil 0.02 mg than in the sufentanil group (0 and 1 respectively, p < 0.05). The median intensity of propofol-induced pain was statistically similar between the groups receiving sufentanil or remifentanil 0.01 mg and the placebo group (1, 1 and 1, respectively, p > 0.05).. Remifentanil 0.02 mg administered over 60 seconds before propofol administration is more effective than sufentanil 0.01 mg, remifentanil 0.01 mg or placebo administered 1 minute prior to propofol in reducing the incidence and intensity of injection pain.

Topics: Adult; Analgesics, Opioid; Anesthetics, Intravenous; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Hypotension; Injections, Intravenous; Middle Aged; Pain; Pain Measurement; Piperidines; Placebos; Propofol; Remifentanil; Sufentanil; Time Factors; Treatment Outcome

To compare the effect of remifentanil combined with desflurane or isoflurane on the quality of the operative field and surgical conditions, blood loss, and recovery during tympanoplasty or endoscopic sinus surgery.. Randomised, double-blinded clinical study.. Sixty-four patients were scheduled for elective tympanoplasty or endoscopic sinus surgery. The patients were randomly divided into two groups: desflurane or isoflurane. After anaesthesia induction, all patients received a continuous remifentanil infusion of 0.2-0.5 microg/kg/min until a mean arterial pressure of 65-75 mmHg was achieved. Heart rate and mean arterial pressure were recorded throughout anaesthesia. Blood loss was measured at the end of surgery. Achievement of a bloodless operative field was rated on a 100 mm visual analogue scale. Following completion of surgery, the time to extubation and to achievement of an Aldrete score of nine or more was recorded.. Sixty-three patients were evaluated. The total dose of remifentanil and the total blood loss were similar in both groups (p > 0.05). Time to extubation and to an Aldrete score of nine or more for the desflurane group was significantly less than for the isoflurane group (p 0.05).. Although desflurane and isoflurane both enabled good surgical conditions (in terms of quality of operative field) and convenient induction of hypotension for tympanoplasty and endoscopic sinus surgery, the recovery characteristics of desflurane were better than those of isoflurane. Therefore, desflurane may be preferable to isoflurane in such circumstances.

Topics: Adolescent; Adult; Anesthesia Recovery Period; Anesthetics, Combined; Blood Loss, Surgical; Desflurane; Double-Blind Method; Endoscopy; Female; Heart Rate; Humans; Hypotension; Isoflurane; Male; Middle Aged; Nasal Polyps; Piperidines; Remifentanil; Sinusitis; Treatment Outcome; Tympanoplasty

To determine the effect of alpha-tocopherol in patients receiving hypotensive anesthesia with propofol-remifentanil.. Prospective, randomized study.. University hospital.. 66 ASA physical status I and II patients, aged 32 to 56 years, scheduled for nasal polypectomy.. Patients were allocated into two groups, the treatment and the control groups (T group and C group). T group received alpha-tocopherol 300 mg orally 5 to 6 hours before surgery.. Sampling times and measurements were done before hypotension (t0), 45 minutes after starting hypotension (t1), 90 minutes after starting hypotension (t2), 45 minutes after recovery of normotension (t3), and 24 hours after surgery (t4). Renal function was assessed by testing glomerular and tubular functions: glomerular filtration rate, fractional excretion of sodium (FENA); fractional excretion of urea (FEUN); and urinary N-acetyl-1-beta-D-glucosoaminidase (NAG) index (NAGi).. Glomerular filtration rate values remained unchanged in all patient populations. Fractional excretion of sodium was within reference ranges in both groups at times t0, t1, and t2. At time t3, a significant FE(NA) peak was observed. At this time, FENA was significantly higher in C group than T group (P < 0.001). FEUN time course was similar to the FENA trend. At time t4, FENA and FEUN returned to basal values. At time t3, NAGi was also increased without significant intergroup differences (P < 0.01, P < 0.001, and P < 0.01 vs times t0, t1, t2 in C group, respectively; P < 0.01, P < 0.01, and P < 0.001 vs times t0, t1, and t2 in T group, respectively).. In patients without any renal disease, hypotensive anesthesia with propofol and remifentanil results in a transient tubular dysfunction, which appears to be minimized by the preoperative administration of alpha-tocopherol.

Topics: Acetylglucosaminidase; Adult; alpha-Tocopherol; Anesthesia, Intravenous; Anesthetics, Intravenous; Antioxidants; Female; Humans; Hypotension; Hypotension, Controlled; Kidney Diseases; Kidney Function Tests; Male; Middle Aged; Piperidines; Propofol; Remifentanil; Sodium; Urea

The purpose of this study was to compare the effects of fentanyl and remifentanil on splanchnic perfusion during coronary artery bypass graft (CABG) surgery. Fifty patients were randomized to receive either fentanyl (10 microgxkg(-1) at induction and 5 microgxkg(-1)xh(-1) infusion for maintenance) or remifentanil (3 microgxkg(-1) at induction and 1 microgxkg(-1)xmin(-1) infusion for maintenance). Patients in both groups were comparable with regard to demographics. Intraoperative volume management and inotropic therapy were similiar in both groups. Regarding heart rate, there were no significant differences between the groups at any measurement time (P > 0.05). Compared to the fentanyl group, the remifentanil group showed a significant decrease in mean arterial pressure during induction. Also, the gastric intramucosal CO(2) pressure (Pg(CO) (2)) and the P(CO) (2)-gap, defined as the difference between Pg(CO) (2) and Pa(CO) (2), were significantly increased and the gastric mucosal pH (pHi) was significantly decreased in the remifentanil group in the postinduction period (P < 0.05). However, there were no statistically significant differences in respiratory data at any time between the two groups (P > 0.05). Both fentanyl and remifentanil seemed to be effective and well tolerated in this CABG population. Episodes of hypotension and transient reduction in splanchnic perfusion were more common in patients treated with remifentanil when compared to those receiving the fentanyl opioid regimen.

Topics: Analysis of Variance; Anesthetics, Intravenous; Blood Pressure; Carbon Dioxide; Coronary Artery Bypass; Female; Fentanyl; Gastric Mucosa; Heart Rate; Humans; Hydrogen-Ion Concentration; Hypotension; Length of Stay; Male; Manometry; Middle Aged; Piperidines; Remifentanil; Respiration; Splanchnic Circulation; Time Factors

In this prospective case-series study, a balanced anesthetic scheme of sevoflurane in nitrous oxide supplemented with remifentanil and sustained neuromuscular block was applied in nine patients scheduled for laparoscopic adrenalectomy for pheochromocytoma. Laparoscopic adrenalectomy to treat pheochromocytoma results in marked catecholamine release during pneumoperitoneum and tumor manipulation. Remifentanil infusion was adjusted to maintain systolic arterial pressure between 120-170 mmHg. Increased infusion rate of remifentanil was used (up to 3 microg/kg/min) to prevent and treat marked hemodynamic changes from catecholamine release during tumor manipulation. Hpotension after tumor removal was treated with additional colloids fluids and decreasing the remifentanil infusion rate by 25-50%.

Topics: Adrenal Gland Neoplasms; Adrenalectomy; Adult; Anesthetics, Inhalation; Anesthetics, Intravenous; Blood Pressure; Catecholamines; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Hypotension; Laparoscopy; Male; Methyl Ethers; Middle Aged; Neuromuscular Blockade; Nitrous Oxide; Pheochromocytoma; Piperidines; Postoperative Nausea and Vomiting; Prospective Studies; Remifentanil; Sevoflurane; Treatment Outcome

Intraoperative combinations of volatile and opioid agents are used to achieve unconsciousness, hypnotic sparing, haemodynamic stability and uneventful recovery. This study describes the influence of different remifentanil concentrations on these variables when combined with desflurane during abdominal surgery.. Sixty-one healthy adult patients were randomly allocated to one of five predefined remifentanil target concentrations (3, 5, 7, 10 or 15 ng ml(-1)). Anaesthesia was titrated to maintain mean blood pressure (MBP), heart rate (HR) and BIS trade mark within predetermined values by adjusting desflurane delivery. Postoperative analgesia using propacetamol and morphine was initiated 30-45 min before skin closure, and continued using morphine PCA.. Desflurane requirements adjusted to both BIS and haemodynamics were not significantly modified by the remifentanil concentration (median Fet(DES) 2.7% before incision, 2.5% intraoperatively, and 2.2% during closure), resulting in a calculated drug consumption of 0.22-0.25 ml min(-1) (with 1.5 l min(-1) fresh gas flow). High remifentanil concentration decreased MBP and HR, and reduced the duration of tachycardia, but increased the duration of hypotension. The optimal balance was obtained with a remifentanil concentration of 5-7 ng ml(-1) for intubation, 3 ng ml(-1) until incision, 10 ng ml(-1) during intra-abdominal surgery and 5-7 ng ml(-1) during closure. Post-operative morphine requirements were not significantly modified by intraoperative remifentanil concentrations (median 30 mg/24 h, range [2-88]).. Remifentanil target concentrations from 3 to 15 ng ml(-1) had little influence on desflurane requirements or postoperative morphine consumption, but markedly modified intraoperative haemodynamic stability, suggesting that the target concentration should closely follow the successive noxious stimulations.

Topics: Abdomen; Acetaminophen; Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Anesthetics, Inhalation; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Desflurane; Electroencephalography; Female; Heart Rate; Humans; Hypotension; Isoflurane; Male; Middle Aged; Morphine; Nitrous Oxide; Piperidines; Recovery of Function; Remifentanil; Tachycardia

This prospective, randomized, double-blinded study was designed to compare the effects of desflurane, isoflurane and sevoflurane when combined with remifentanil for induced hypotension on surgical conditions and operative field during tympanoplasty.. Sixty patients undergoing tympanoplasty were enrolled in the study. The patients were randomized into three groups of 20 each to receive the inhalation anaesthetics desflurane, isoflurane or sevoflurane. Propofol 2 mg kg(-1) was administered for induction of anaesthesia in all groups. All patients received a continuous infusion of remifentanil which was titrated between 0.2 and 0.5 microg kg(-1) min(-1) to achieve a mean blood pressure (BP) of 60-70 mmHg. Nitroglycerine was infused if this BP could not be achieved. Arterial pressures were recorded continuously throughout the operation. Surgical conditions were assessed every 20 min by the blinded surgeon using a six-point category scale (0-5).. One patient in the desflurane group and two patients in isoflurane group required nitroglycerine to maintain desired mean BP. Sustained controlled hypotension was sufficient in all of the groups throughout surgery. Category scale scores were < or =3 throughout the study, except one patient in the sevoflurane group who had a score of 4 at the 60th minute of the operation. No difference was found among groups when haemodynamic parameters and surgical category scale scores were compared. There were no postoperative respiratory and circulatory complications.. Desflurane, sevoflurane or isoflurane combined with remifentanil provided adequate induced hypotension and similar operating conditions and any of them could be safely and equally used in anaesthesia for tympanoplasty.

Topics: Adolescent; Adult; Analgesics, Opioid; Anesthetics, Combined; Anesthetics, Inhalation; Anesthetics, Intravenous; Blood Pressure; Desflurane; Double-Blind Method; Female; Humans; Hypotension; Isoflurane; Male; Methyl Ethers; Middle Aged; Nitroglycerin; Piperidines; Propofol; Prospective Studies; Remifentanil; Sevoflurane; Tympanoplasty; Vasodilator Agents

At present, there is no proven pharmacologic treatment for cognitive or language impairments in Down syndrome (DS). Cholinergic deficits have been documented in DS and linked to cognitive deficits. This study is a 24-week open-label clinical trial of donepezil hydrochloride for the treatment of language deficits in adults with DS. To our knowledge, this is the first prospective study to evaluate systematically the effects of donepezil, a cholinesterase inhibitor, on specific language domains in DS. The main finding that emerged was an improvement in expressive language performance following donepezil therapy. Despite the multiple methodological limitations, the results raise important questions regarding the role of the cholinergic system in language function and the specific effect of cholinergic therapy in the treatment of language impairment in DS. The results support the need for large-scale controlled studies of the effects of donepezil treatment on language and on other cognitive domains in DS.

Topics: Adult; Appetite; Cholinesterase Inhibitors; Diarrhea; Donepezil; Dose-Response Relationship, Drug; Down Syndrome; Female; Follow-Up Studies; Humans; Hypotension; Indans; Language Disorders; Language Tests; Male; Muscle Cramp; Nausea; Piperidines; Treatment Outcome

Remifentanil is a potent ultra-short-acting opioid, which permits rapid emergence. However, remifentanil is expensive and may have detrimental effects on hemodynamics in case of overdose. Target-controlled infusion (TCI) permits adapting infusion to pharmacokinetic models. In this prospective randomized study, we compared intra- and postoperative hemodynamics, remifentanil requirement during anesthesia, and postoperative morphine requirement in patients scheduled for carotid surgery, and receiving either continuous IV weight-adjusted infusion of remifentanil (RIVA) or TCI for remifentanil (TCIR). Forty-six patients were enrolled in this study: all were anesthetized by using TCI for propofol. Twenty-three received RIVA (0.5 micro g. kg(-1) x min(-1)) for the induction of anesthesia and endotracheal intubation, with the infusion rate decreased to 0.25 micro g x kg(-1) x min(-1) after intubation, then adapted by step of 0.05 micro g x kg(-1) x min(-1) according to hemodynamics. Twenty-three patients received TCIR (Minto model, Rugloop), with an effect-site concentration at 4 ng/mL during induction, then adapted by step of 1 ng/mL according to hemodynamics. All patients received atracurium and a 50% mixture of N(2)O/O(2). Hemodynamic variables were recorded each minute. The number and duration of hemodynamic events were collected, and total doses of anesthetics (remifentanil and propofol) and vasoactive drugs were noted in both groups of patients. Data were analyzed by using unpaired t-tests. RIVA was significantly associated with more frequent episodes of intraoperative hypotension (16 versus 6, P < 0.001) and more frequent episodes of postoperative hypertension and/or tachycardia requiring more frequent administration of beta-adrenergic blockers (16 vs 10, P < 0.04) in comparison with TCIR. The need for morphine titration was not significantly different between groups. TCIR led to a significantly smaller requirement of remifentanil (700 +/- 290 versus 1390 +/- 555 micro g, P < 0.001) without difference in propofol requirement. This prospective randomized study demonstrated that, during carotid endarterectomy, in comparison with patients receiving remifentanil using continuous RIVA, TCI results in less hypotensive episodes during the induction of anesthesia, in fewer episodes of tachycardia and/or hypertension and a smaller beta-adrenergic blocker requirement during recovery, and a decrease in remifentanil requirement. Recommendations to prefer TCI for remif. Remifentanil for intraoperative analgesia in carotid artery surgery is associated with a better stability in perioperative hemodynamics when administered in target-controlled infusion compared with continuous weight-adjusted infusion. This may be related to a smaller requirement of this drug when using target-controlled infusion, as well as a smooth mode of administration.

Topics: Adrenergic beta-Antagonists; Aged; Analgesics, Opioid; Anesthesia, General; Endarterectomy, Carotid; Endpoint Determination; Female; Hemodynamics; Humans; Hypotension; Infusions, Intravenous; Male; Monitoring, Intraoperative; Pain, Postoperative; Piperidines; Postoperative Complications; Prospective Studies; Remifentanil; Vascular Surgical Procedures

The aim of this prospective, randomized study was to compare the preparation and discharge times, the side-effects and patient satisfaction after gynaecological outpatient procedures performed using either spinal block or total intravenous anaesthesia with propofol and remifentanil.. With Ethics Committee approval and written informed consent, 40 healthy females scheduled for hysteroscopic ablation of endometrial neoplasm were randomly allocated to receive either a spinal block with bupivacaine 0.5% hyperbaric solution 10 mg (n = 20) or total intravenous anaesthesia with propofol and remifentanil (n = 20). Preparation and discharge times, as well as occurrence of untoward events and anaesthesia-related costs, were recorded.. The median (range) preparation time was 7 (7-10) min with general anaesthesia, and 11 (7-21) min with spinal block (P = 0.00005). No differences in discharge time from the postanaesthesia care unit and incidence of hypotension or bradycardia, or both, were reported between the two groups. Hospital discharge times were 156 (101-345) min after general anaesthesia and 296 (195-720) min after spinal anaesthesia (P = 0.0005). Acceptance of the anaesthesia technique was better after general (100%) than after spinal anaesthesia (75%) (P = 0.04). No differences in total costs were reported between spinal block ([symbol: see text] 155 ([symbol: see text] 117-[symbol: see text] 224)) and propofol-remifentanil general anaesthesia ([symbol: see text] 143 ([symbol: see text] 124-[symbol: see text] 203) (P = 0.125)).. Accurate titration of short-acting intravenous anaesthetic drugs such as propofol and remifentanil results in shorter preparation times and earlier home discharge after outpatient gynaecological procedures compared with spinal anaesthesia with hyperbaric bupivacaine 10 mg, with better patient acceptance and no increased costs.

Topics: Adult; Aged; Ambulatory Surgical Procedures; Anesthesia, Spinal; Anesthetics, Combined; Anesthetics, Intravenous; Anesthetics, Local; Bupivacaine; Female; Gynecologic Surgical Procedures; Humans; Hypotension; Length of Stay; Middle Aged; Patient Satisfaction; Piperidines; Propofol; Prospective Studies; Remifentanil

This prospective randomized study investigated the influence of normotensive and hypotensive general anesthesia on platelet aggregability, intraoperative blood loss and parameters of plasmatic coagulation during extensive orthognathic surgery. A total of 30 patients were randomly allocated for either normotensive anesthesia maintained by continuous infusion of propofol and remifentanil (NORMO, n=10) or hypotensive anesthesia, whereby hypotension was induced by increasing the infusion rate of remifentanil (HYPO-R, n=10) or by administration of nitroglycerin (HYPO-N, n=10). Whole blood platelet aggregability was significantly reduced during hypotension compared to normotensive anesthesia (P<.01, HYPO-N and HYPO-R vs. NORMO). Mean arterial blood pressure during hypotension correlated well with adenosinediphosphate- (R=.712, P<.001) and collagen-induced platelet aggregability (R=.685, P<.001). Within hypotensive study groups, postoperative fibrinogen levels were significantly different, whereas intraoperative platelet aggregability, postoperative platelet count, prothrombin time, activated partial thromboplastin time and antithrombin levels were not different. Normotensive anesthesia, however, caused significant decreases in platelet count (-29%), prothrombin time (-24%), fibrinogen (-41%) and antithrombin (-28%) and a significant prolongation in activated partial thromboplastin time (+21%) and thrombin time (+18%). There was a trend to reduced intraoperative blood loss in hypotensive study groups; however, differences were not significant. In conclusion, induced hypotension--independent of substances used for induction of hypotension--reduces intraoperative platelet aggregability, subsequently protecting the coagulation system against subclinical consumption coagulopathy. Induced hypotension-caused platelet dysfunction does not lead to an increased intraoperative blood loss, but quite on the contrary shows a trend to reduced intraoperative blood loss, possibly by preventing platelet-induced subclinical consumption coagulopathy.

Topics: Adult; Anesthesia; Anesthetics, Intravenous; Biomarkers; Blood Loss, Surgical; Female; Hemostasis; Humans; Hypotension; Male; Nitroglycerin; Oral Surgical Procedures; Piperidines; Platelet Aggregation; Propofol; Remifentanil

We compared the hemodynamic effects of a bolus administration of 1 microg/kg remifentanil for 1, 3, and 5 min (1, 0.33, and 0.2 microg. kg(-1). min(-1), respectively) in patients scheduled for coronary artery bypass grafting anesthetized with small-dose propofol. The study was terminated after only eight patients had been enrolled (three received remifentanil at a rate of 1.0 microg. kg(-1). min(-1), two at 0.33 microg. kg(-1). min(-1), and three at 0.2 microg. kg(-1). min(-1)) because of severe hemodynamic instability, which was particularly marked in four patients and consisted of severe bradycardia in one patient and severe hypotension with a reduction in systemic vascular resistance in three others. One patient showed evidence of myocardial ischemia. All patients responded to therapeutic interventions. The results show that remifentanil should be given only by slow infusion to such patients.. This study investigates the effect on the heart and blood vessels of various rates of administration of boluses of a relatively new potent opiate, remifentanil, to patients with coronary artery disease. The results show that remifentanil should be given only by slow infusion to such patients.

Topics: Anesthetics, Intravenous; Bradycardia; Coronary Artery Bypass; Depression, Chemical; Hemodynamics; Humans; Hypotension; Piperidines; Remifentanil

Topics: Anesthesia, General; Female; Humans; Hypotension; Isonipecotic Acids; Meperidine; Nitriles; Pain, Postoperative; Perphenazine; Piperidines; Postoperative Complications; Sleep; Sterilization, Tubal

The search for new drugs remains an important focus for the safe and effective treatment of cardiovascular diseases. Previous evidence has shown that choline analogs can offer therapeutic benefit for cardiovascular complications. The current study investigates the effects of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol (LQFM032) on cardiovascular function and cholinergic-nitric oxide signaling. Synthesized LQFM032 (0.3, 0.6, or 1.2 mg/kg) was administered by intravenous and intracerebroventricular routes to evaluate the potential alteration of mean arterial pressure, heart rate, and renal sympathetic nerve activity of normotensive and hypertensive rats. Vascular function was further evaluated in isolated vessels, while pharmacological antagonists and computational studies of nitric oxide synthase and muscarinic receptors were performed to assess possible mechanisms of LQFM032 activity. The intravenous and intracerebroventricular administration of LQFM032 elicited a temporal reduction in mean arterial pressure, heart rate, and renal sympathetic nerve activity of rats. The cumulative addition of LQFM032 to isolated endothelium-intact aortic rings reduced vascular tension and elicited a concentration-dependent relaxation. Intravenous pretreatment with L-NAME (nitric oxide synthase inhibitor), atropine (nonselective muscarinic receptor antagonist), pirenzepine, and 4-DAMP (muscarinic M1 and M3 subtype receptor antagonist, respectively) attenuated the cardiovascular effects of LQFM032. These changes may be due to a direct regulation of muscarinic signaling as docking data shows an interaction of choline analog with M1 and M3 but not nitric oxide synthase. Together, these findings demonstrate sympathoinhibitory, hypotensive, and antihypertensive effects of LQFM032 and suggest the involvement of muscarinic receptors.

Topics: Animals; Antihypertensive Agents; Aorta, Thoracic; Atropine; Blood Pressure; Heart Rate; Hypertension; Hypotension; Male; Muscarinic Antagonists; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Piperazines; Piperidines; Pirenzepine; Pyrazoles; Rats, Inbred SHR; Rats, Wistar; Receptor, Muscarinic M1; Receptor, Muscarinic M3

Paravertebral block (PVB) is feasible for postoperative analgesia in patients who undergo cardiac surgery with unilateral thoracotomy. Postoperative continuous PVB is as effective as thoracic epidural anesthesia and is less likely to cause hypotension. However, the intraoperative utility and safety of PVB remains unclear. Therefore, the present study was conducted to determine the efficacy and hemodynamic influence of intraoperative paravertebral bolus injection during cardiac surgery. We retrospectively compared intraoperative medication use and blood pressure measurements between patients who underwent transapical transcatheter aortic valve implantation (TA-TAVI) with (PVB group, n = 46) or without (non-PVB group, n = 15) intraoperative PVB. Remifentanil administration was lower by more than 40 % in the PVB group compared with that in the non-PVB group (728 ± 319 µg vs. 1240 ± 488 µg, P < 0.001). The average and variability of intraoperative blood pressure showed no significant differences between groups. The duration of hypotension (blood pressure less than 80 % of baseline) was 25.1 ± 21.5 % and 25.4 ± 18.1 % of the entire anesthesia time in the non-PVB and PVB groups, respectively (P = 0.74). The use of inotropic and vasopressor agents was comparable between groups. Intraoperative paravertebral bolus injection decreased remifentanil administration without causing hypotension during TA-TAVI in hemodynamically unstable patients. This result suggests the intraoperative utility of PVB in cardiac surgery.

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Anesthetics, Local; Aortic Valve; Blood Pressure; Bupivacaine; Cardiac Catheterization; Cardiotonic Agents; Female; Fentanyl; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Hypotension; Levobupivacaine; Male; Nerve Block; Pain; Pain Measurement; Piperidines; Remifentanil; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vasoconstrictor Agents

Remifentanil stimulates the parasympathetic nervous system, and patients with increased parasympathetic tone may be at greater risk of bradycardia after its administration. We aimed to establish if adult patients with increased baseline parasympathetic tone were at higher risk of bradycardia and hypotension when given a bolus dose of remifentanil. Seventy adults (age 20-60 years and ASA physical status 1 or 2) were given remifentanil 1 μg.kg(-1) . A Holter ECG monitor was used to assess heart rate changes. Heart rate variability in the frequency domain during the 5 min after remifentanil administration was analysed. Multivariate analysis demonstrated that baseline heart rate was the only independent predictor of remifentanil-induced bradycardia [odds ratio (95% CI) 0.877 (0.796-0.966)]. The vagotonic action of remifentanil does not appear to be related to baseline autonomic tone in adult patients.

Topics: Adult; Anesthetics, Intravenous; Autonomic Nervous System; Blood Pressure; Bradycardia; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Hypotension; Male; Middle Aged; Piperidines; Remifentanil; Young Adult

Histamine, acting centrally as a neurotransmitter, evokes a reversal of hemorrhagic hypotension in rats due to the activation of the sympathetic and the renin-angiotensin systems as well as the release of arginine vasopressin and proopiomelanocortin-derived peptides. We demonstrated previously that central nicotinic cholinergic receptors are involved in the pressor effect of histamine. The aim of the present study was to examine influences of centrally administrated histamine on acetylcholine (ACh) release at the posterior hypothalamus-a region characterized by location of histaminergic and cholinergic neurons involved in the regulation of the sympathetic activity in the cardiovascular system-in hemorrhage-hypotensive anesthetized rats. Hemodynamic and microdialysis studies were carried out in Sprague-Dawley rats. Hemorrhagic hypotension was induced by withdrawal of a volume of 1.5 ml blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP), heart rate (HR), and an increase in extracellular posterior hypothalamic ACh and choline (Ch) levels by 56% and 59%, respectively. Intracerebroventricularly (i.c.v.) administered histamine (50, 100, and 200 nmol) dose- and time-dependently increased MAP and HR and caused an additional rise in extracellular posterior hypothalamic ACh and Ch levels at the most by 102%, as compared to the control saline-treated group. Histamine H1 receptor antagonist chlorpheniramine (50 nmol; i.c.v.) completely blocked histamine-evoked hemodynamic and extracellular posterior hypothalamic ACh and Ch changes, whereas H2 and H3/H4 receptor blockers ranitidine (50 nmol; i.c.v.) and thioperamide (50 nmol; i.c.v.) had no effect. In conclusion, centrally administered histamine, acting via H1 receptors, increases ACh release at the posterior hypothalamus and causes a pressor and tachycardic response in hemorrhage-hypotensive anesthetized rats.

Topics: Acetylcholine; Animals; Blood Pressure; Chlorpheniramine; Choline; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Rate; Hemorrhage; Histamine; Histamine Agonists; Histamine Antagonists; Hypotension; Hypothalamus, Posterior; Male; Microdialysis; Piperidines; Rats; Rats, Sprague-Dawley; Time Factors

A patient under medication for depression underwent orthopedic surgery for osteoarthritis of the knee four times. For the second surgery, general anesthesia was induced with propofol, remifentanil, and rocuronium. Immediately after induction, she developed severe hypotension that was resistant to vasopressors. The hypotension likely resulted from the effect of psychotropic drugs, including levomepromazine, olanzapine, and clomipramine, which she had been receiving for a long time. Although her blood pressure recovered, the surgery was cancelled. We performed spinal anesthesia for the subsequent surgery to minimize interactions between anesthetic and psychotropic agents. A continuous infusion of the local anesthetic bupivacaine through a epidural catheter was started during the surgery. Although her general condition was stable during surgery, she developed hypotension after returning to the ward. We suspected an interaction with the psychotropic agents, and thus stopped infusion of the local anesthetic, after which, her blood pressure gradually increased. The first and fourth surgeries were performed uneventfully under spinal anesthesia. This case suggests that anesthesiologists should pay special attention to the interaction between anesthetic and psychotropic agents during anesthesia. Further, psychotropic drug withdrawal before surgery should be considered, if possible. Moreover, vasopressin may be utilized to treat catecholamine-resistant hypotension.

Topics: Anesthesia, Epidural; Anesthesia, General; Anesthesia, Local; Anesthesia, Spinal; Anesthetics, Local; Antidepressive Agents; Blood Pressure; Bupivacaine; Female; Humans; Hypotension; Middle Aged; Piperidines; Propofol; Remifentanil

Combination of local and regional anesthetic agents are widely used in emergency and surgical setting and the interaction between the medications used in general anesthesia and these local and/or regional anesthetic becomes a growing concern in current patient management system. The interaction between general anesthetic agents and the local anesthetic agents given epidurally, spinally, intravenously or intramuscularly and the effects of BIS monitorisation on combined propofol-remifentanil anesthesia are examined in several studies. In literature, there is no research investigating the effect of lidocaine infusion on remifentanil and anesthetic dosage used in hypotensive anesthesia. The aim of this study is to examine this effect.. We studied 39, ASA I-II patients undergoing elective transsphenoidal endoscopic hypophyseal adenoma excision procedure. After preoperative examination and informed consent of the patient, monitorisation with non invasive blood pressure measurement, electrocardiography, pulse oxymeter and Bispectral Index (BIS) was performed. 0.9% NaCl infusion was started via a 20 G route. Lidocaine (1%) was given as 1.5 mg.kg(-1) hour-1 infusion after 1.5 mg.kg(-1) bolus dosage given in 10 minutes. Lidocaine infusion was started at the same time with anesthesia induction and was stopped after surgery. 0.9% NaCl was given as bolus dosage and as infusion in control group. Induction was maintained via propofol (1%) with 10 mg (1 ml) doses given in 5 seconds and it was applied in every 15 seconds until BIS < 45'. During maintenance of anesthesia desflurane-remifentanil-oxygen (50%)-air (50%) mixture was used. Desflurane was titrated by BIS measurement between 40 and 5012. Remifentanil infusion was started after propofol induction with 0.1 µg.kg(-1).min(-1) dosage and it was titrated between 0.1-0.5 µg.kg(-1).min(-1) levels. For intubation, rocuronium with 0.8 mg kg(-1) dosage was given during induction. After the surgical procedure, it was antagonised with neostigmine and atropine. For postoperative analgesia 1 g paracetamole was given IV after the surgery within 15 minutes and it was reapplied with 1 gr doses in every 6 hours. After extubation, the pain of the patients was examined at 15. minute at the recovery room with VRS (VRS; 0-no pain, 1-slight pain, 2-moderate pain, 3-severe pain). If VRS was greater than 2, 50 mg dolantine was given IM. For prevention of nausea and vomitting, 8 mg ondansetron was given IV. Perioperative total doses of remifentanil, desflurane (ml) (anesthesia machine records) and lidocaine (mg) were recorded after the surgery. Perioperative hemodynamic parameters (systolic, diastolic, mean blood pressures, heart rates) were recorded after monitorisation (basal), after intubation, after the start of the surgery and after extubation.. There were no statistically significant difference between two groups with respect to patient characteristics (age, gender, weight, length, Basal Mass Index = BMI) (p > 0.05). The duration of anesthesia and surgery were also not different statistically (p > 0.05). There were no statistically significant difference between two groups with respect to remifentanil dose (p > 0.05). There were no statistically significant difference between two groups with respect to eye opening and extubation times (p > 0.05). When usage rates and amounts of dolantine, paracetamole and novalgine were compared, we found no statistically significant difference between two groups (p > 0.05). Basal mean arterial blood pressure measurements of the patients and mean arterial blood pressure measurements of the patients after induction, after intubation, 1 minute, 5 minutes, 10 minutes, 15 minutes after discharge of surgery and after extubation showed no statistically significant difference (p > 0.05). Basal heart rate measurements and the heart rates after induction, after intubation, 1 minute, 5 minutes, 10 minutes, 15 minutes after discharge of surgery and after extubation showed no statistically significant difference (p > 0.05). Basal BIS measurements and BIS measurements after induction, after intubation, 1 minute, 5 minutes, 10 minutes, 15 minutes after discharge of surgery and after extubation showed no statistically significant difference (p > 0.05).. We found no statistically significant difference between two groups about different parameters. But new investigations with different local anesthetic agents may show sigificant difference and usage of these local anesthetic agents may be advised.

Topics: Adenoma; Adolescent; Adult; Aged; Anesthetics, Combined; Anesthetics, Intravenous; Anesthetics, Local; Blood Pressure; Blood Pressure Monitors; Consciousness Monitors; Drug Administration Schedule; Electrocardiography; Endoscopy; Female; Heart Rate; Humans; Hypotension; Infusions, Parenteral; Intraoperative Neurophysiological Monitoring; Lidocaine; Male; Middle Aged; Operative Time; Oximetry; Pain, Postoperative; Piperidines; Pituitary Neoplasms; Predictive Value of Tests; Remifentanil; Time Factors; Treatment Outcome; Young Adult

Some agonists of ghrelin receptors cause rapid decreases in BP. The mechanisms by which they cause hypotension and the pharmacology of the receptors are unknown.. The effects of ligands of ghrelin receptors were investigated in rats in vivo, on isolated blood vessels and on cells transfected with the only molecularly defined ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR1a).. Three agonists of GHSR1a receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP in the anaesthetized rat. The effect was not reduced by either of two GHSR1a antagonists, JMV2959 or YIL781, at doses that blocked effects on colorectal motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated ghrelin or the unacylated ghrelin receptor agonist, AZP531. The early hypotension preceded a decrease in sympathetic nerve activity. Early hypotension was not reduced by hexamethonium or by baroreceptor (sino-aortic) denervation. Ulimorelin also relaxed isolated segments of rat mesenteric artery, and, less potently, relaxed aorta segments. The vascular relaxation was not reduced by JMV2959 or YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected HEK293 cells at nanomolar concentrations. JMV2959 and YIL781 both antagonized effects in these cells, with their pA2 values at the GHSR1a receptor being 6.55 and 7.84.. Our results indicate a novel vascular receptor or receptors whose activation by ulimorelin, capromorelin and CP464709 lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not activated by ghrelin.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Ghrelin; HEK293 Cells; Humans; Hypotension; In Vitro Techniques; Macrocyclic Compounds; Male; Mesenteric Arteries; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Ghrelin

We report the case of a patient who underwent surgical aortic valve replacement. During general anaesthesia maintenance, the patient received a remifentanyl infusion via a target controlled infusion (TCI) system. The infusion pump that was prepared to deliver the infusion showed malfunction at the beginning of the surgery, so it was quickly replaced with a second pump. After a few minutes into the surgery, the patient presented with hypotension refractory to treatment. The remifentanyl syringe also emptied faster than expected. On reviewing the TCI pump, it was found that it was erroneously programmed for propofol instead of remifentanyl, thus the patient had received a very high dose of remifentanyl that was probably the cause of the haemodynamic disturbances. The incident was an error in equipment use, facilitated by hurry, lack of checking of the equipment prior to its use, and the complex and unclear design of the devices' screens. After analysis of this incident, all TCI pumps were reviewed, and all the programs for infrequently used drugs were deleted. Furthermore, 2 pumps were selected for exclusive use in the cardiac surgery theatre, one with propofol-only programming, and the other with remifentanyl-only programming, both clearly marked and situated in fixed places in that theatre.

Topics: Anesthetics, General; Aortic Valve; Drug Overdose; Equipment Failure; Equipment Failure Analysis; Heart Valve Prosthesis Implantation; Humans; Hypotension; Infusion Pumps; Intraoperative Complications; Male; Medication Errors; Piperidines; Propofol; Remifentanil; Risk Management

Patients undergoing surgery in beach chair position (BCP) are at risk of cerebral ischaemia. We determined the prevalence and risk factors of jugular venous bulb oxygen desaturation (SjvO(2)  < 50%) in BCP. It was also examined whether regional cerebral tissue oxygen saturation (SctO(2) ) measured by near-infrared spectroscopy and SjvO(2) are interchangeable for assessment of cerebral oxygenation.. Fifty-six consecutive patients undergoing arthroscopic shoulder surgery in BCP were studied. Anaesthesia was intravenous with propofol and remifentanil (P/R) or inhalational with sevoflurane and 50% nitrous oxide (S/N) depending on provider choice. Mean arterial pressure (MAP), heart rate (HR), SjvO(2) , and SctO(2) were measured before (baseline; post-induction in supine position) and after the patients assumed BCP. Bland-Altman analysis was performed to measure the agreement between SctO(2) and SjvO(2) .. SjvO(2) , SctO(2) , MAP, and HR decreased significantly when patients were raised into BCP. Jugular desaturation occurred in 41% of patients (56% with P/R vs. 21% with S/N anaesthesia, P = 0.0077). Risk factors for the desaturation included P/R anaesthesia [adjusted odds ratio (aOR) 4.76, 95% confidence interval (CI) 1.34-16.95, P = 0.016] and MAP < 50 mmHg (aOR 3.85, 95% CI 1.21-12.25, P = 0.023). Bland-Altman analysis showed a mean difference of -8.9% with 95% limit of agreement between -40.0% and 23.0%. The percentage error [1.96 standard deviation/mean of the reference method] was 48.5%.. The incidence of jugular desaturation in BCP was 41%, and P/R anaesthesia and hypotension were associated with its occurrence while undergoing surgery under general anaesthesia. SctO(2) may not replace SjvO(2) for the determination of cerebral oxygenation.

Topics: Aged; Anesthesia, General; Anesthesia, Inhalation; Anesthesia, Intravenous; Anesthetics, Inhalation; Anesthetics, Intravenous; Arthroscopy; Brain; Elective Surgical Procedures; Female; Hemodynamics; Humans; Hypotension; Hypoxia, Brain; Intraoperative Complications; Jugular Veins; Male; Methyl Ethers; Middle Aged; Monitoring, Intraoperative; Nitrous Oxide; Oximetry; Oxygen; Piperidines; Posture; Propofol; Remifentanil; Sevoflurane; Shoulder Joint

The experiments employing high-frequency ultrasonic technique and selective blockers of M1, M3, and M4 muscarinic cholinergic receptors pirenzepine, 4-DAMP, and tropicamide, respectively, revealed individual roles of these receptors in the development of severe posthemorrhagic hypotension in rats with low or high individual resistance to circulatory hypoxia. The study showed that M1 and M4 muscarinic receptors are involved in shock-limiting and shock-activating processes, respectively, while M3 receptors exert no effect on the course of posthemorrhagic abnormalities in systemic and hepatic portal circulation and on the posthemorrhagic lifespan. Poor resistance of the cardiovascular system to circulatory hypoxia during shock development is considered to be dysregulatory pathology.

Topics: Animals; Blood Circulation; Blood Pressure; Hemorrhage; Hypotension; Male; Muscarinic Antagonists; Piperidines; Pirenzepine; Rats; Rats, Wistar; Receptor, Muscarinic M1; Receptor, Muscarinic M3; Receptor, Muscarinic M4; Tropicamide

We investigated the effects of the beach-chair position and induced hypotension on regional cerebral oxygen saturation (rSO(2)) in patients undergoing arthroscopic shoulder surgery by using near-infrared spectroscopy.. Twenty-eight patients scheduled for arthroscopic shoulder surgery were enrolled prospectively. After induction of anesthesia, mechanical ventilation was controlled to maintain Paco(2) at 35 to 40 mm Hg. Anesthesia was maintained with sevoflurane and remifentanil. After radial artery cannulation, mean arterial pressure (MAP) was measured at the external auditory meatus level and maintained between 60 and 65 mm Hg. The rSO(2) was measured by use of near-infrared spectroscopy. MAP and rSO(2) were recorded at the following times: before induction (T(0)), immediately after induction (T(1) [baseline]), after beach-chair position (T(2)), immediately after induced hypotension (T(3)), 1 hour after induced hypotension (T(4)), and after supine position at the end of surgery (T(5)). Cerebral desaturation was defined as a reduction in rSO(2) to less than 80% of baseline value for 15 seconds or greater.. A total of 27 patients were evaluated until the end of this study. The MAP at T(2) was significantly lower than that at T(1). The MAP values at T(3) and T(4) were significantly lower than those at T(1) and T(2). The rSO(2) at T(2) was significantly lower than that at T(1). Unlike the pattern of change in the MAP, there was no additional decrease in rSO(2) at T(3) and T(4). There were 2 patients who had an episode of cerebral desaturation.. The beach-chair position combined with induced hypotension significantly decreases rSO(2) in patients undergoing shoulder arthroscopic surgery under general anesthesia.. Level IV, study of nonconsecutive patients without consistently applied reference gold standard.

Topics: Aged; Anesthesia, General; Arthroscopy; Blood Pressure; Cerebrovascular Circulation; Cognition; Female; Humans; Hypotension; Male; Middle Aged; Oxygen; Piperidines; Postoperative Complications; Postoperative Period; Posture; Preoperative Period; Prospective Studies; Remifentanil; Shoulder; Spectroscopy, Near-Infrared

The concept of opioid-induced hyperalgesia has recently gained prominence as a contributing factor for long-term treatment failure.. To evaluate possible differences of opioids used in anaesthesia, cumulative doses of sufentanil and remifentanil were compared with escalating doses of the oripavine derivative etorphine, in awake and trained canines. This was followed by naloxone unmasking a possible hyperalgesic state, which had developed during opioid administration. Heart rate, blood pressure and propagation of nociceptive volleys in somatosensory-evoked potentials as well as the skin-twitch reflex were evaluated.. Opioid-related hypotension and bradycardia were reversed by naloxone with a late (30 min) overshoot of R43 and R17% after remifentanil and sufentanil, respectively. Following etorphine, overshoot in mean blood pressure was R9%, whereas heart rate still remained below S9% when compared with control. Peak hyperalgesia, as detected in the somatosensory-evoked potential and skin-twitch, increased by R70% after remifentanil and by R43% after sufentanil. This reflected a significant (P<0.005) increase in propagation of nociceptive afferents as late as 30 min after naloxone reversal. Such potentiation was not observed in the etorphine group, as peak somatosensory-evoked potential deflection and skin-twitch remained below S80% when compared with control.. The pure mu-agonists sufentanil or remifentanil seem to induce a 'bimodal' inhibitory followed by an excitatory effect. The latter is unmasked by naloxone in the postadministration period. In contrast, this is not seen with etorphine, a close congener of buprenorphine. The proposed mode of action of such hyperexcitatory effects may involve second-messenger-mediated G-protein activation, originally proposed by others. Ligands of the oripavine series may present an alternative for prevention of opioid-induced hyperalgesia in patients.

Topics: Afferent Pathways; Analgesics, Opioid; Animals; Blood Pressure; Bradycardia; Dogs; Dose-Response Relationship, Drug; Etorphine; Evoked Potentials, Somatosensory; Heart Rate; Hyperalgesia; Hypotension; Naloxone; Narcotic Antagonists; Piperidines; Remifentanil; Substance Withdrawal Syndrome; Sufentanil

To report our experience of providing anesthesia for noncardiac procedures in children with in situ Berlin Heart EXCOR Pediatric ventricular assist devices and to suggest principles of anesthetic management.. With the initiation of the first North American training and support center for Berlin Heart at our institution in 2006, we have been asked to provide anesthesia for noncardiac procedures to these children. No current anesthetic approach to these children has been reported.. Anesthetic records for all noncardiac procedures for children with Berlin Heart between August 2006 and February 2009 in a tertiary care pediatric hospital were retrospectively reviewed. Charts were reviewed for demographic and clinical data, perioperative management, and occurrence of hypotension.. Twenty-nine procedures were performed on 11 patients. Hypotension was a common occurrence with all anesthetic induction and maintenance agents even at low doses. Ketamine induction, however, was less likely to produce hypotension, odds ratio for hypotension 0.1333 (95% confidence range 0.021-0.856). Hypotension was responsive to fluid bolus (60%) and alpha-receptor agonists (100%). Preoperative stability and presence of biventricular ventricular assist device (BiVAD) did not predict intraoperative hemodynamic course.. Unlike patients with other ventricular assist devices, these children do not tolerate reductions in systemic vascular resistance (SVR) because of the relatively fixed cardiac output of this device. Agents that reduce SVR should be avoided where possible. Preoperative stability is not predictive. Fluids and alpha-agonists should be first-line response to hypotension in this population. Further study of this unusual population is warranted to further delineate best anesthetic practice.

Topics: Adolescent; Adult; Anesthesia; Anesthetics, Dissociative; Anesthetics, Intravenous; Child; Child, Preschool; Female; Heart-Assist Devices; Humans; Hypotension; Infant; Intraoperative Complications; Ketamine; Male; Odds Ratio; Piperidines; Remifentanil; Retrospective Studies; Surgical Procedures, Operative; Young Adult

The authors aimed to test the hypothesis that xenon anesthesia limits adverse hypotensive effects of losartan during acute hemorrhage. In six conscious unsedated Beagle dogs, the systemic and pulmonary circulation were monitored invasively, and two subsequent 60-min hypotensive challenges were performed by (a) induction (propofol) and maintenance of anesthesia with isoflurane/remifentanil or xenon/remifentanil and by (b) subsequent hemorrhage (20 mL kg⁻¹ within 5 min) from a central vein. The same amount of blood was retransfused 1 h after hemorrhage. Experiments were performed with or without acute angiotensin II receptor subtype 1 blockade by i.v. losartan (100 μg·kg⁻¹·min⁻¹) starting 45 min before induction of anesthesia. Four experiments were performed in each individual dog. Xenon/remifentanil anesthesia provided higher baseline mean arterial blood pressure (85 ± 6 mmHg) than isoflurane/remifentanil anesthesia (67 ± 3 mmHg). In losartan-treated animals, isoflurane/remifentanil caused significant hypotension (42 ± 4 mmHg for isoflurane/remifentanil vs. 71 ± 6 mmHg for xenon/remifentanil). Independent of losartan, hemorrhage did not induce any further reduction of mean arterial blood pressure or cardiac output in either group. Spontaneous hemodynamic recovery was observed in all groups before retransfusion was started. Losartan did not alter the adrenaline, noradrenaline, and vasopressin response to acute hemorrhage. Losartan potentiates hypotension induced by isoflurane/remifentanil anesthesia but does not affect the hemodynamic stability during xenon/remifentanil anesthesia. Losartan does not deteriorate the hemodynamic adaptation to hemorrhage of 20 mL kg⁻¹ during xenon/remifentanil and isoflurane/remifentanil anesthesia. Therefore, xenon/remifentanil anesthesia protects against circulatory side effects of losartan pretreatment and thus may afford safer therapeutic use of losartan during acute hemorrhage.

Topics: Anesthesia; Angiotensin Receptor Antagonists; Animals; Blood Pressure; Dogs; Female; Hemodynamics; Hemorrhage; Hypotension; Losartan; Piperidines; Remifentanil; Xenon

During shoulder arthroscopy in the beach-chair position, cerebral ischemia may be a serious complication because prolonged hypotension may affect regional cerebral oxygen supply. We present the cases of 2 patients in whom a reduction in mean arterial pressure after anesthesia provoked a decrease in frontal lobe oxygenation to below the level that causes presyncopal symptoms in the awake subject. In the healthy middle-aged patient, cerebral oxygenation decreased by approximately 40%, indicating that cerebral blood flow was markedly reduced, and intravenous administration of ephedrine rapidly restored cerebral oxygenation. During surgery in the beach-chair position, hypotension must be avoided, and in all patients regional, cerebral oxygenation should be monitored and optimized.

Topics: Anesthesia, General; Arthroscopy; Blood Gas Monitoring, Transcutaneous; Brain Ischemia; Cerebrovascular Circulation; Ephedrine; Frontal Lobe; Humans; Hypotension; Hypoxia, Brain; Intraoperative Complications; Male; Middle Aged; Monitoring, Intraoperative; Piperidines; Posture; Propofol; Remifentanil; Rotator Cuff; Rotator Cuff Injuries

It is widely assumed that LPS lowers arterial pressure during sepsis by stimulating release of TNF-alpha and other vasoactive mediators from macrophages. However, recent data from this and other laboratories have shown that LPS hypotension can be prevented by inhibiting afferent impulse flow in the vagus nerve, by blocking neuronal activity in the nucleus of the solitary tract, or by blocking alpha-adrenergic receptors in the preoptic area/anterior hypothalamic area (POA). These findings suggest that the inflammatory signal is conveyed from the periphery to the brain via the vagus nerve, and that endotoxic shock is mediated through a central mechanism that requires activation of POA neurons. In the present study, we tested whether central cannabinoid 1 (CB1) receptors participate in the control of arterial pressure during endotoxemia based on evidence that hypothalamic neurons express CB1 receptors and synthesize the endogenous CB anandamide. We found that intracerebroventricular administration of rimonabant, a CB1 receptor antagonist, inhibited the fall in arterial pressure evoked by LPS significantly in both conscious and anesthetized rats. Rimonabant attenuated both the immediate fall in arterial pressure evoked by LPS and the second, delayed hypotensive phase that leads to tissue ischemia and death. Rimonabant also prevented the associated LPS-induced rise in extracellular fluid norepinephrine concentrations in the POA. Furthermore, rimonabant attenuated the associated increase in plasma TNF-alpha concentrations characteristic of the late phase of endotoxic hypotension. These data indicate that central CB1 receptors may play an important role in the initiation of endotoxic hypotension.

Topics: Animals; Anterior Hypothalamic Nucleus; Arachidonic Acids; Blood Pressure; Endocannabinoids; Endotoxins; Hypotension; Lipopolysaccharides; Macrophages; Male; Neurons; Norepinephrine; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Rimonabant; Tumor Necrosis Factor-alpha

Vascular hyporeactivity, which occurs in the terminal stage of hemorrhagic shock, is believed to be critical for treating hemorrhagic shock. The present study was designed to examine whether the CB1 cannabinoid receptor (CB1R) was involved in the development of vascular hyporeactivity in rats suffering from hemorrhagic shock.. Sixteen animals were randomly divided into two groups (n = 8 in each group): sham-operated (Sham) and hemorrhagic shock (HS) groups. Hemorrhagic shock was induced by bleeding. The mean arterial pressure (MAP) was reduced to and stabilized at (25 +/- 5) mmHg for 2 hours. The vascular reactivity was determined by the response of MAP to norepinephrine (NE). In later experiments another twelve animals were used in which the changes of CB1R mRNA and protein in aorta and superior mesenteric artery (SMA) were analyzed by RT-PCR and Western blotting. In addition, we investigated the effects of a CB1R antagonist on the vascular hyporeactivity and survival rates in rats with hemorrhagic shock. Survival rates were analyzed by the Fisher's exact probability test. The MAP response was analyzed by one-way analysis of variance (ANOVA).. Vascular hyporeactivity developed in all animals suffering from hemorrhagic shock. The expression of CB1R mRNA and protein in aorta and 2 - 3 branches of the SMA were significantly increased in the HS group after the development of vascular hyporeactivity when compared to those in Sham group. When SR141716A or AM251 was administered, the MAP response to NE was (41.75 +/- 4.08) mmHg or (44.78 +/- 1.80) mmHg respectively, which was higher than that in saline groups with (4.31 +/- 0.36) mmHg (P < 0.01). We also showed an increased 4-hour survival rate in the SR141716A or AM251-treated group with 20% or 30%, but with a statistically significant difference present between the AM251-treated and saline groups (P < 0.05).. CB1R is involved in vascular hyporeactivity resulting from hemorrhagic shock in rats, and CB1R antagonist may be useful in treating patients with traumatic, hemorrhagic shock who need field-rescue or initial treatment.

Topics: Animals; Blotting, Western; Gene Expression Regulation; Hypotension; Male; Piperidines; Pyrazoles; Random Allocation; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Reverse Transcriptase Polymerase Chain Reaction; Rimonabant; Shock, Hemorrhagic; Survival Rate

Topics: Adult; Anesthesia, General; Anesthetics, Intravenous; Bradycardia; Bronchial Spasm; Cholinesterase Inhibitors; Drug Interactions; Drug Therapy, Combination; Humans; Hypotension; Male; Myasthenia Gravis; Piperidines; Preanesthetic Medication; Propofol; Pyridostigmine Bromide; Remifentanil; Thymectomy

Topics: Aged; Anesthesia, Intravenous; Atracurium; Electromyography; Entropy; Ephedrine; Humans; Hypotension; Infusions, Intravenous; Male; Neuromuscular Blocking Agents; Piperidines; Propofol; Remifentanil

A paradoxical microcirculatory constriction has been observed in hearts of patients with ischemia, secondary to coronary stenosis. Here, using the isolated mouse heart (Langendorff), we examined the mechanism of this response, assuming involvement of nitric oxide (NO) and endothelin-1 (ET-1) systems. Perfusion pressure was maintained at 65 mmHg for 70 min (protocol 1), or it was reduced to 30 mmHg over two intervals, between the 20- and 40-min marks (protocol 2) or from the 20-min mark onward (protocol 3). In protocol 1, coronary resistance (CR) remained steady in untreated heart, whereas it progressively increased during treatment with the NO synthesis inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME) (2.7-fold) or the ET(A) antagonist BQ-610 (2.8 fold). The ET(B) antagonist BQ-788 had instead no effect by itself but curtailed vasoconstriction to BQ-610. In protocol 2, hypotension raised CR by 2.2-fold. This response was blunted by reactive oxygen species (ROS) scavengers (mannitol and superoxide dismutase plus catalase) and was converted into vasodilation by l-NAME, BQ-610, or BQ-788. Restoration of normal pressure was followed by vasodilation and vasoconstriction, respectively, in untreated and treated preparations. In protocol 3, CR progressively increased with hypotension in the absence but not presence of L-NAME or BQ-610. We conclude that the coronary vasculature is normally relaxed by two concerted processes, a direct action of NO and ET-1 curtailing an ET(B2)-mediated tonic vasoconstriction through ET(A) activation. The negative feedback mechanism on ET(B2) subsides during hypotension, and the ensuing vasoconstriction is ascribed to ET-1 activating ET(A) and ET(B2) and reactive nitrogen oxide species originating from ROS-NO interaction.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Coronary Stenosis; Coronary Vessels; Endothelins; Enzyme Inhibitors; Hemodynamics; Hypotension; Mice; Mice, Inbred C57BL; Microcirculation; Models, Cardiovascular; Myocardial Ischemia; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oligopeptides; Piperidines; Reactive Oxygen Species; Vasoconstriction; Vasodilation; Vasomotor System

Series of thiazoles, triazoles, and imidazoles were designed as bioisosteres, based on the 1,5-diarylpyrazole motif that is present in the potent CB(1) receptor antagonist rimonabant (SR141716A, 1). A number of target compounds was synthesized and evaluated in cannabinoid (hCB(1) and hCB(2)) receptor assays. The thiazoles, triazoles, and imidazoles elicited in vitro( )()CB(1) antagonistic activities and in general exhibited considerable CB(1) vs CB(2) receptor subtype selectivities, thereby demonstrating to be cannabinoid bioisosteres of the original diarylpyrazole class. Some key representatives in the imidazole series showed potent pharmacological in vivo activities after oral administration in both a CB agonist-induced hypotension model and a CB agonist-induced hypothermia model. Molecular modeling studies showed a close three-dimensional structural overlap between the key compound 62 and rimonabant. A structure-activity relationship (SAR) study revealed a close correlation between the biological results in the imidazole and pyrazole series.

Topics: Administration, Oral; Animals; CHO Cells; Cricetinae; Cricetulus; Cyclohexanols; Hypotension; Hypothermia; Imidazoles; Mice; Models, Molecular; Molecular Conformation; Piperidines; Pyrazoles; Radioligand Assay; Rats; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Rimonabant; Stereoisomerism; Structure-Activity Relationship; Thiazoles; Triazoles

Topics: Anesthetics, Inhalation; Anesthetics, Intravenous; Child; Humans; Hypotension; Intraoperative Complications; Laminectomy; Male; Methyl Ethers; Piperidines; Propofol; Remifentanil; Rubinstein-Taybi Syndrome; Sevoflurane

Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand of the cannabinoid CB(1) and CB(2) receptors. CB(1) receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioral effects of anandamide are antinociception, catalepsy, hypothermia, and depression of motor activity, similar to Delta(9)-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study, we looked at the possible role of the CB(1) receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP(8-37) was also able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide inhibition was reversed by the CB(1) receptor antagonist AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both presynaptically, to prevent CGRP release from trigeminal sensory fibers, and postsynaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB(1) receptors seem to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a noncannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system.

Topics: Animals; Arachidonic Acids; Blood Pressure; Calcitonin Gene-Related Peptide; Capsaicin; Electric Stimulation; Endocannabinoids; Hypotension; Male; Neurons; Nitroprusside; Pain; Peptide Fragments; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Trigeminal Caudal Nucleus; Vasodilation

Endocannabinoids and CB1 receptors have been implicated in endotoxin (LPS)-induced hypotension: LPS stimulates the synthesis of anandamide in macrophages, and the CB1 antagonist SR-141716 inhibits the hypotension induced by treatment of rats with LPS or LPS-treated macrophages. Recent evidence indicates the existence of cannabinoid receptors distinct from CB1 or CB2 that are inhibited by SR-141716 but not by other CB1 antagonists such as AM251. In pentobarbital-anesthetized rats, intravenous injection of 10 mg/kg LPS elicited hypotension associated with profound decreases in cardiac contractility, moderate tachycardia, and an increase in lower body vascular resistance. Pretreatment with 3 mg/kg SR-141716 prevented the hypotension and decrease in cardiac contractility, slightly attenuated the increase in peripheral resistance, and had no effect on the tachycardia caused by LPS, whereas pretreatment with 3 mg/kg AM251 did not affect any of these responses. SR-141716 also elicited an acute reversal of the hypotension and decreased contractility when administered after the response to LPS had fully developed. The LPS-induced hypotension and its inhibition by SR-141716 were similar in pentobarbital-anesthetized wild-type, CB1(-/-), and CB1(-/-)/CB2(-/-) mice. We conclude that SR-141716 inhibits the acute hemodynamic effects of LPS by interacting with a cardiac receptor distinct from CB1 or CB2 that mediates negative inotropy and may be activated by anandamide or a related endocannabinoid released during endotoxemia.

Topics: Animals; Cannabinoids; Endotoxins; Heart; Heart Rate; Hemodynamics; Hypotension; Male; Mice; Mice, Knockout; Myocardial Contraction; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Rimonabant; Vascular Resistance

Our objective was to identify the sites of interaction of cannabinoids with cardiovascular sympathetic regulation in the rat. Effects on sympathetic tone were first determined in anaesthetised animals following i.v. administration of the drugs. Central effects were evaluated in anaesthetised rats receiving microinjections of cannabinoids into brain stem nuclei. Peripheral effects were identified in pithed rats with electrically stimulated sympathetic outflow. In anaesthetised and artificially ventilated rats, i.v. injection of the cannabinoid agonists WIN55212-2 and CP55940 decreased mean arterial pressure, heart rate and the plasma noradrenaline concentration. These effects were antagonized by the CB(1) cannabinoid receptor antagonist SR141716A. The bradycardia was abolished by the muscarinic acetylcholine receptor antagonist methylatropine. The decreases in mean arterial pressure and heart rate caused by cannabinoids in ventilated rats were much less pronounced than in spontaneously breathing rats. Microinjection of WIN55212-2 into the nucleus tractus solitarii had no effect. Microinjected into the rostral ventrolateral medulla oblongata, WIN55212-2 lowered mean arterial pressure slightly without changing other parameters. In pithed rats, WIN55212-2 inhibited the increases in mean arterial pressure, heart rate and the plasma noradrenaline concentration evoked by electrical stimulation of the sympathetic outflow. Our results show that activation of CB(1) cannabinoid receptors induces sympathoinhibition and enhancement of cardiac vagal tone, leading to hypotension and bradycardia. Presynaptic inhibition of noradrenaline release from terminals of postganglionic sympathetic neurons is the major component of the sympathoinhibition, but an effect in the rostral ventrolateral medulla oblongata may also contribute. The cannabinoid-evoked cardiovascular depression depends strongly on the respiratory state of the animals.

Topics: Animals; Atropine Derivatives; Benzoxazines; Bradycardia; Cannabinoids; Cardiovascular System; Cyclohexanols; Disease Models, Animal; Dose-Response Relationship, Drug; Hypotension; Male; Medulla Oblongata; Microinjections; Morpholines; Naphthalenes; Norepinephrine; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Rimonabant; Sympathetic Fibers, Postganglionic; Sympathetic Nervous System

Topics: Anesthetics, Intravenous; Humans; Hypotension; Infusions, Intravenous; Piperidines; Remifentanil

In the present study, we examined cardiac and regional haemodynamic effects of endothelin-1 (ET-1), a potent vasoconstrictive factor, in a rat model of pressure-controlled irreversible haemorrhagic shock resulting in the death of all control animals within 30 min. Experiments were carried out in male ethylurethane-anaesthetised Wistar rats subjected to hypotension of 20-25 mmHg, which resulted in bradycardia, an extreme decrease in cardiac index (CI) and an increase in total peripheral resistance index (TPRI), with reductions in renal (RBF), hindquarters (HBF) and mesenteric blood flow (MBF). ET-1 (50, 200 pmol/kg) administered intravenously at 5 min of critical hypotension produced increases in mean arterial pressure (MAP) and heart rate (HR), which were significantly higher than those in normotensive animals, and a 100% survival at 2 h after treatment. The effects were accompanied by a rise in CI, a decrease in TPRI, with increases in RBF and HBF and persistently lowered MBF, and an increase in circulating blood volume 20 min after treatment. The cardiovascular effects of ET-1 were inhibited by the ETA receptor antagonist BQ-123 (1 mg/kg), while the ETB receptor antagonist BQ-788 (3 mg/kg) had no effect. In conclusion, ET-1 acting via ETA receptors produces reversal of haemorrhagic hypotension in rats due to the mobilisation of blood from venous reservoirs, with the improvements in cardiac function and the perfusion of peripheral tissues.

Topics: Animals; Blood Pressure; Bradycardia; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; Hemodynamics; Hemorrhage; Hindlimb; Hypotension; Injections, Intravenous; Male; Oligopeptides; Peptides, Cyclic; Piperidines; Rats; Rats, Wistar; Receptor, Endothelin A; Renal Circulation; Shock, Hemorrhagic; Sodium Chloride; Splanchnic Circulation; Time Factors; Vascular Resistance

In hypertensive subjects, a single bout of dynamic exercise results in an immediate lowering of blood pressure back toward normal. This postexercise hypotension (PEH) also occurs in the spontaneously hypertensive rat (SHR). In both humans and SHRs, PEH features a decrease in sympathetic nerve discharge, suggesting the involvement of central nervous system pathways. Given that substance P is released in the nucleus tractus solitarius (NTS) by activation of baroreceptor and skeletal muscle afferent fibers during muscle contraction, we hypothesized that substance P acting at neurokinin-1 (NK-1) receptors in the NTS might contribute to PEH. We tested the hypothesis by determining, in conscious SHRs, whether NTS microinjections of the NK-1 receptor antagonist SR-140333 before exercise attenuated PEH. The antagonist, in a dose (60 pmol) that blocked substance P- and spared D,L-homocysteic acid-induced depressor responses, significantly attenuated the PEH by 37%, whereas it had no effect on blood pressure during exercise. Vehicle microinjection had no effect. The antagonist also had no effect on heart rate responses during both exercise and the PEH period. The data suggest that a substance P (NK-1) receptor mechanism in the NTS contributes to PEH.

Topics: Animals; Blood Pressure; Consciousness; Hypertension; Hypotension; Male; Microinjections; Neurokinin-1 Receptor Antagonists; Physical Exertion; Piperidines; Quinuclidines; Rats; Rats, Inbred SHR; Solitary Nucleus

Remifentanil hydrochloride is an ultra-short-acting opioid that undergoes rapid metabolism by tissue and plasma esterases. We aimed to characterize the pharmacokinetics and determine the hemodynamic profile of remifentanil after a single-bolus dose in children aged 0 to 18 yr. Forty-two children undergoing elective surgical procedures received remifentanil 5 microg/kg infused over 1 min. Patients were divided into age groups as follows: young infants (< or =2 mo), older infants (> 2 mo to < 2 yr), young children (2 to < 7 yr), older children (7 to < 13 yr), adolescents (13 to < 16 yr), and young adults (16 to < 18 yr). Arterial blood samples were collected and analyzed by mass spectroscopy to determine remifentanil pharmacokinetic profiles. Hemodynamic measurements for remifentanil's effect were made after the infusion. Methods of statistical analysis included analysis of variance and linear regression, with significance at P < or = 0.05. Complete remifentanil pharmacokinetic data were obtained from 34 patients. The volume of distribution was largest in the infants < 2 mo (mean, 452 mL/kg) and decreased to means of 223 to 308 mL/kg in the older patients. There was a more rapid clearance in the infants < 2 mo of age (90 mL. kg(-1). min(-1)) and infants 2 mo to 2 yr (92 mL. kg(-1). min(-1)) than in the other groups (means, 46 to 76 mL. kg(-1). min(-1)). The half-life was similar in all age groups, with means of 3.4 to 5.7 min. Seven subjects (17%) developed hypotension related to the remifentanil bolus. Remifentanil showed an extremely rapid elimination similar to that in adults. The fast clearance rates observed in neonates and infants, as well as the lack of age-related changes in half-life, are in sharp contrast to the pharmacokinetic profile of other opioids. Remifentanil in a bolus dose of 5 microg/kg may cause hypotension in anesthetized children.. The pharmacokinetics of remifentanil were studied in children from birth to 18 yr. Remifentanil was found to have age-related changes in clearance and volume of distribution, but not half-life. The increased clearance observed in young infants is in contrast to other opioids.

Topics: Adolescent; Analgesics, Opioid; Anesthesia; Anesthetics, Intravenous; Blood Pressure; Child; Child, Preschool; Elective Surgical Procedures; Female; Heart Rate; Humans; Hypotension; Infant; Infant, Newborn; Linear Models; Male; Piperidines; Remifentanil

Carotid endarterectomy can be performed under general or locoregional anesthesia. If locoregional anesthesia is chosen, the state of awareness of the patient allows for direct viewing of the effect of vascular clamping of the corresponding neurological territory. We present the results of an anesthetic procedure using only an analgesic in patients who were intubated and ventilated but with a level of consciousness that allowed us to view the effect of carotid clamping on motor functions.. Forty-eight patients, ASA II-III, underwent surgical carotid endarterectomy. The anesthetic protocol began with preoxygenation for 2 min; induction with remifentanil 0.75-1 microgram kg-1 for 2 min., followed by perfusion of 1 microgram/kg-1.min-1 of remifentanil and propofol 1 microgram/kg-1; and orotracheal intubation by local anesthesia of the glottis with 5% lidocaine spray. Ventilation was with FiO2 100%, FR 12 min. and VT 8 ml. kg-1. For maintenance the dose of remifentanil was regulated to obtain a coordinated motor response (maximum 1.5 microgram/kg-1.min-1, minimum 0.35 microgram/kg-1. min-1). For all patients we monitored hemodynamics continuously and non-invasively, including aortic output by the transesophageal Doppler echocardiography.. The objective of anesthesia was reached in all the patients. The most common hemodynamic alterations were bradycardia (28), arterial hypotension (25), elevated blood pressure (3) and altered aortic output. All changes were corrected quickly with the treatment used, guided by the evolution of hemodynamic parameters. Postanesthetic recovery came in less than 4 min. The only episodes of hyper -and hypotension consisted of a few episodes of mild hyper- (12) and hypotension (1), which were soon corrected. No alterations attributable to hemodynamic instability occurred. During surgery, an intracarotid shunt was necessary in only one patient. Three suffered surgically-related neurological complications after the operations. No complications could be attributed to anesthesia.. An advantage of this technique is that the duration of anesthesia is not limited, with adequate ventilation and maintenance of an adequate state of consciousness for clinical evaluation of the repercussions of carotid clamping. Hemodynamic monitoring detected the appearance of imbalances requiring therapeutic intervention. The procedure is interesting provided it is performed according to a strict protocol, with continuous clinical and instrumental monitoring of the patient's status.

Topics: Aged; Aged, 80 and over; Alprazolam; Anesthesia Recovery Period; Anesthesia, Intravenous; Anesthetics, Intravenous; Bradycardia; Cardiac Output; Endarterectomy, Carotid; Female; Hemodynamics; Humans; Hydroxyzine; Hypnotics and Sedatives; Hypotension; Intraoperative Complications; Male; Middle Aged; Monitoring, Intraoperative; Piperidines; Postoperative Complications; Preanesthetic Medication; Propofol; Remifentanil; Treatment Outcome

Cannabinoids, including the endogenous ligand anandamide, elicit pronounced hypotension and bradycardia through the activation of CB1 cannabinoid receptors. A second endogenous cannabinoid, 2-arachidonoyl glycerol (2-AG), has been proposed to be the natural ligand of CB1 receptors. In the present study, we examined the effects of 2-AG on mean arterial pressure and heart rate in anesthetized mice and assessed the role of CB1 receptors through the use of selective cannabinoid receptor antagonists and CB1 receptor knockout (CB1(-/-)) mice. In control ICR mice, intravenous injections of 2-AG or its isomer 1-AG elicit dose-dependent hypotension and moderate tachycardia that are unaffected by the CB1 receptor antagonist SR141716A. The same dose of SR141716A (6 nmol/g IV) completely blocks the hypotensive effect and attenuates the bradycardic effect of anandamide. 2-AG elicits a similar hypotensive effect, resistant to blockade by either SR141716A or the CB2 antagonist SR144528, in both CB1(-/-) mice and their homozygous (CB1(+/+)) control littermates. In ICR mice, arachidonic acid (AA, 15 nmol/g IV) elicits hypotension and tachycardia, and indomethacin (14 nmol/g IV) inhibits the hypotensive effect of both AA and 2-AG. Synthetic 2-AG incubated with mouse blood is rapidly (<2 minutes) and completely degraded with the parallel appearance of AA, whereas anandamide is stable under the same conditions. A metabolically stable ether analogue of 2-AG causes prolonged hypotension and bradycardia in ICR mice, and both effects are completely blocked by SR141716A, whereas the same dose of 2-AG-ether does not influence blood pressure and heart rate in CB1(-/-) mice. These findings are interpreted to indicate that exogenous 2-AG is rapidly degraded in mouse blood, probably by a lipase, which masks its ability to interact with CB1 receptors. Although the observed cardiovascular effects of 2-AG probably are produced by an arachidonate metabolite through a noncannabinoid mechanism, the CB1 receptor-mediated cardiovascular effects of a stable analogue of 2-AG leaves open the possibility that endogenous 2-AG may elicit cardiovascular effects through CB1 receptors.

Topics: Anesthesia; Animals; Arachidonic Acids; Blood Pressure; Camphanes; Cardiovascular Agents; Cardiovascular Diseases; Dose-Response Relationship, Drug; Endocannabinoids; Female; Glycerides; Heart Rate; Hypotension; Indomethacin; Ligands; Male; Mice; Mice, Inbred ICR; Mice, Knockout; Piperidines; Pyrazoles; Receptors, Cannabinoid; Receptors, Drug; Rimonabant; Tachycardia

The cardiovascular response to 5-hydroxytryptamine (5-HT) challenge has been previously described in cattle. Abrupt bradycardia, followed by tachycardia, triphasic systemic blood pressure response, and pulmonary hypertension were the major changes elicited by 5-HT. The purpose of the present study was to determine whether the cardiovascular response to 5-HT in calves was attributable to 5-HT2 receptors. A specific 5-HT2 antagonist (metrenperone, 0.05 mg/kg) was administered intramuscular to six unsedated Friesian calves 30 min before the animals were given a 5-min intravenous 5-HT infusion. Mean systemic arterial (SAP), mean pulmonary arterial (PAP), pulmonary capillary wedge (PW) pressures were obtained by means of fluid-filled catheters, and cardiac output (CO) was measured by the thermodilution technique. Heart rate, stroke volume, systemic (SVR) and pulmonary (PVR) vascular resistances were calculated. Administration of 5-HT after metrenperone induced a short-lasting period of severe bradycardia followed by tachycardia and increased CO. The systemic blood pressure response was exclusively hypotensive and associated with a decrease in SVR. Conversely, PAP, PW, and PVR were not modified by 5-HT administration. The results establish that 5-HT induced systemic as well as pulmonary hypertension is mediated through the activation of type-2 serotonergic or alpha-adrenergic receptors, or both. In contrast, neither apnoea, bradycardia and hypotension, nor the positive chronotropic effect induced by 5-HT in cattle are mediated through such receptors.

Topics: Animals; Body Temperature; Bradycardia; Cardiovascular System; Cattle; Hypotension; Kinetics; Muscle, Skeletal; Piperidines; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Sleep Stages

1. This study attempts to investigate if endogenous nitric oxide (NO) can modulate the eicosanoid-releasing properties of intravenously administered endothelin-1 (ET-1) in the pulmonary and circulatory systems in the guinea-pig. 2. The nitric oxide synthase blocker N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM; 30 min infusion) potentiated, in an L-arginine sensitive fashion, the release of thromboxane A2 (TxA2) stimulated by ET-1, the selective ET(B) receptor agonist IRL 1620 (Suc-[Glu9,Ala11,15]-ET-1(8-21)) or bradykinin (BK) (5, 50 and 50 nM, respectively, 3 min infusion) in guinea-pig isolated and perfused lungs. 3. In anaesthetized and ventilated guinea-pigs intravenous injection of ET-1 (0.1-1.0 nmol kg(-1)), IRL 1620 (0.2-1.6 nmol kg(-1)), BK (1.0-10.0 nmol kg(-1)) or U 46619 (0.2-5.7 nmol kg(-1)) each induced dose-dependent increases in pulmonary insufflation pressure (PIP). Pretreatment with L-NAME (5 mg kg(-1)) did not change basal PIP, but increased, in L-arginine sensitive manner, the magnitude of the PIP increases (in both amplitude and duration) triggered by each of the peptides (at 0.25, 0.4 and 1.0 nmol kg(-1), respectively), without modifying bronchoconstriction caused by U 46619 (0.57 nmol kg(-1)). 4. The increases in PIP induced by ET-1, IRL 1620 (0.25 and 0.4 nmol kg(-1), respectively) or U 46619 (0.57 nmol kg(-1)) were accompanied by rapid and transient increases of mean arterial blood pressure (MAP). Pretreatment with L-NAME (5 mg kg(-1); i.v. raised basal MAP persistently and, under this condition, subsequent administration of ET-1 or IRL 1620, but not of U-46619, induced hypotensive responses which were prevented by pretreatment with the cyclo-oxygenase inhibitor indomethacin. 5. Thus, endogenous NO appears to modulate ET-1-induced bronchoconstriction and pressor effects in the guinea-pig by limiting the peptide's ability to induce, possibly via ET(B) receptors, the release of TxA2 in the lungs and of vasodilatory prostanoids in the systemic circulation. Furthermore, it would seem that these eicosanoid-dependent actions of ET-1 in the pulmonary system and on systemic arterial resistance in this species are physiologically dissociated.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Airway Resistance; Animals; Antihypertensive Agents; Arginine; Blood Pressure; Bradykinin; Bronchoconstriction; Cyclooxygenase Inhibitors; Drug Synergism; Eicosanoids; Endothelin-1; Endothelins; Enzyme Inhibitors; Female; Guinea Pigs; Hypotension; In Vitro Techniques; Indomethacin; Lung; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oligopeptides; Peptide Fragments; Perfusion; Piperidines; Thromboxane A2; Vasoconstrictor Agents

Macrophages are the primary cellular targets of bacterial lipopolysaccharide (LPS), but the role of macrophage-derived cytokines in LPS-induced septic shock is uncertain. Recent evidence indicates that activation of peripheral CB1 cannabinoid receptors contributes to hemorrhagic hypotension and that macrophage-derived anandamide as well as unidentified platelet-derived substances may be contributing factors. Here we demonstrate that rat platelets contain the endogenous cannabinoid 2-arachidonyl glyceride (2-AG), as identified by reverse phase high-performance liquid chromatography, gas chromatography, and mass spectrometry, and that in vitro exposure of platelets to LPS (200 microg/ml) markedly increases 2-AG levels. LPS-stimulated, but not control, macrophages contain anandamide, which is undetectable in either control or LPS-stimulated platelets. Prolonged hypotension and tachycardia are elicited in urethane-anesthetized rats treated 1) with LPS (15 mg/kg i.v.); 2) with macrophages plus platelets isolated from 3 ml of blood from an LPS-treated donor rat; or 3) with rat macrophages or 4) platelets preincubated in vitro with LPS (200 microg/ml). In all four cases, the hypotension but not the tachycardia is prevented by pretreatment of the recipient rat with the CB1 receptor antagonist SR141716A (3 mg/kg i.v.), which also inhibits the hypotensive response to anandamide or 2-AG. The hypotension elicited by LPS-treated macrophages or platelets remains unchanged in the absence of sympathetic tone or after blockade of nitric oxide synthase. These findings indicate that platelets and macrophages generate different endogenous cannabinoids, and that both 2-AG and anandamide may be paracrine mediators of endotoxin-induced hypotension via activation of vascular CB1 receptors.

Topics: Animals; Arachidonic Acids; Blood Platelets; Cannabinoids; Cells, Cultured; Dronabinol; Endocannabinoids; Glycerides; Hypotension; Lipopolysaccharides; Macrophages; Male; Nitric Oxide; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Drug; Rimonabant

Hypertensive pregnant rats with inhibition of NO synthase are frequently considered as model of pre-eclampsia with proteinuria, hypertension and elevated endothelin (ET-1) blood levels. We describe here the cardiovascular in vivo effects of ET-1 in this rat model since ET-1 and NO are both important vasoactive mediators in uteroplacental circulation. From day 13 of gestation 2 groups of Wistar female rats were fed control (C) or nitroarginine enriched diet (0.063%, Treated: T). On gestational day 20 mean arterial pressure (MAP, mmHg) was measured via a carotid catheter in pentobarbital (60 mg/kg) anesthetized rats. After chronic NO synthase inhibition hypertension develops; MAP on day 20: 158 +/- 2.2 in T and 113 +/- 2.2 in C, p < 0.001. ET-1 bolus injection (0.1 nmol/kg) is rapidly followed by a decrease in blood pressure significantly more important in T: -46 +/- 5.1 than in C: -30 +/- 2.2. In vivo depressor effect is blocked by the specific antagonist BQ-788. After inhibition of cycloxygenase with acetylsalicylic acid (27 mumol/kg, 30 min before) the hypotension is not modified. Since NO and PGI2 productions are not expected in our conditions, vasodepressor effect can be explained by an endothelial hyperpolarazing factor (EDHF). In conclusion in vivo ET-1 hypotensive effects in pregnant rats are mediated by ETB receptors and more pronounced in hypertensive NO-deprived animals.

Topics: Animals; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Female; Hypotension; Nitric Oxide Synthase; Oligopeptides; Piperidines; Pre-Eclampsia; Pregnancy; Pregnancy, Animal; Rats; Rats, Wistar

1. The effects of the selective and potent novel platelet-activating factor (PAF) antagonist, UR-12633 (1-(3,3-diphenylpropionyl)-4-(3-pyridylcyanomethyl)piperidin e) on several markers of endotoxic shock syndrome were evaluated in rats and mice. 2. UR-12633, administered 60 min after E. coli lipopolysaccharide (LPS), reversed the LPS-induced sustained hypotension in rats at doses of 0.01 to 1 mg kg-1, i.v. The reference compound WEB-2086 (1 mg kg-1) also reversed the LPS-induced hypotension. UR-12633 (1 mg kg-1), administered 10 min before LPS, almost fully inhibited sustained hypotension. The immediate hypotension (within 1 min) caused by LPS was not prevented by either UR-12633 or WEB-2086. 3. Pretreatment with 10 mg kg-1, i.v. of either UR-12633 or WEB-2086 inhibited the increase in disseminated intravascular coagulation markers, such as activated partial thromboplastin time (55 and 74% inhibition, respectively), and prothrombin time (22 and 72% inhibition) and prevented the decrease in plasma fibrinogen content (100 and 29% inhibition). 4. Increases in acid phosphatase (ACP) plasma activity, a marker of lysosomal activation, and in lactate dehydrogenase (LDH), a marker of tissue damage, were inhibited by pretreatment with 10 mg kg-1, i.v. of either UR-12633 or WEB-2086 (100% and 69% inhibition, ACP; 62 and 48% inhibition, LDH). Hyperglycaemia (71 and 46%) and hyperlactacidaemia (92 and 56%) were also inhibited. 5. UR-12633, but not WEB-2086, inhibited the LPS-induced increase in vascular permeability in rats, as shown by prevention of haemoconcentration and, to a lesser degree, the increase in Evans blue dye extravasation. 6. In a series of nine reference compounds and UR-12633, we found a high correlation (P < 0.001) between PAF antagonist activity, measured as the inhibition of PAF-induced rabbit platelet aggregation or PAF-induced mortality in mice and the inhibition of LPS-induced mortality. 7. In spite of the multifactorial nature of endotoxic shock, in which many mediators may be involved, the new potent PAF antagonist, UR-12633, proved effective in protecting against changes in most shock markers. These data strongly suggest a key role for PAF in the pathogenesis of endotoxic shock in rodents.

Topics: Analysis of Variance; Animals; Azepines; Blood Pressure; Cell Membrane; Disease Models, Animal; Escherichia coli; Hypotension; Lipopolysaccharides; Male; Mice; Piperidines; Platelet Aggregation Inhibitors; Rabbits; Rats; Rats, Sprague-Dawley; Shock, Septic; Triazoles

Vascular NK-1 and NK-2 tachykinin receptors in the rat and the guinea pig were characterized pharmacologically by using available agonists and antagonists exhibiting varying degrees of selectivity for these receptors. Because the anesthetized guinea pig has unusually low blood pressure, these animals were pithed and vagotomized and infused, throughout the experimental procedure, with norepinephrine (6 micrograms/kg/min). This treatment raised their blood pressure to a level appropriate for the determination of dose-hypotensive response curves. The NK-1 receptor agonists substance P (SP) and septide (0.004 to 1 microgram/kg iv) decreased carotid artery blood pressure in a dose-dependent manner in both species, but they were more potent (13- and 33-fold, respectively) in guinea pigs than in rats. The NK-2 receptor agonist [beta Ala8]-NKA(4-10) (0.06 to 1 microgram/kg) also dose-dependently lowered blood pressure in the pithed guinea pig with noradrenaline-supported blood pressure, although it failed to do so in the same rat preparation. RP 67580, a selective NK-1 antagonist, antagonized the SP- or septide-induced hypotensive response in rats, but not in guinea pigs. Conversely, RPR 100893, a novel NK-1 receptor antagonist chemically related to RP 67580, dose-dependently inhibited hypotension induced by SP, and even more, that induced by septide only in guinea pigs. In the latter species, neither RP 67580 nor RPR 100893 affected decreases in blood pressure induced by [beta Ala8]-NKA(4-10). These decreases were, however, inhibited by the NK-2 receptor antagonist SR 48968. The selectivity of this compound for the latter receptor was confirmed by its failure to affect SP- or septide-induced hypotension in either guinea pigs or rats. These results confirm that the hypotensive responses to SP and septide are mediated by NK-1 receptors in the two species studied. However, functional NK-2 receptors appear to be present in the vascular bed of the guinea pig but not that of the rat, since in the former species the hypotensive responses induced [beta Ala8]-NKA(4-10) were inhibited by SR 48968 but not by the NK-1 receptor antagonists studied. This conclusion is, to our knowledge, drawn here for the first time from clear-cut pharmacological results.

Topics: Animals; Benzamides; Blood Pressure; Guinea Pigs; Hypotension; Indoles; Isoindoles; Male; Neurokinin A; Neurokinin-1 Receptor Antagonists; Peptide Fragments; Piperidines; Pyrrolidonecarboxylic Acid; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Substance P

1. We investigated the effects of the selective endothelin (ET)A receptor antagonist BQ-485 and the selective ETB receptor antagonist BQ-788 on circulatory failure, multiple organ dysfunction syndrome (MODS) and the alterations in acid base balance caused by endotoxaemia in the anaesthetized rat. 2. Male Wistar rats were anaesthetized (thiopentone sodium; 120 mg kg-1, i.p.) and received a continuous infusion of vehicle (saline, 0.6 ml kg-1h-1, i.v.), BQ-485 (10 nmol kg-1 min-1, i.v.) or BQ-788 (10 nmol kg-1 min-1, i.v.). Fifteen min later, animals received a bolus injection of either saline (0.9% NaCl, 1 ml kg-1, i.v.) or E. coli lipopolysaccharide (LPS, 10 mg kg-1, i.v.). 3. Injection of LPS resulted in a fall in blood pressure from 115 +/- 4 mmHg (time 0) to 82 +/- 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the pressor responses to noradrenaline (NA, 1 microgram kg-1, i.v.). Infusion of BQ-788 attenuated the delayed hypotension (at 360 min: 100 +/- 4 mmHg, n = 7; P < 0.05) and significantly enhanced the pressor responses elicited by NA (at 60 to 240 min). In contrast, treatment of LPS-rats with BQ-485 augmented the hypotension (at 360 min), but did not affect the vascular hyporeactivity elicited by endotoxaemia. 4. Endotoxaemia for 360 min resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), glutamate-oxalate-transferase (GOT) and glutamate-pyruvate-transferase (GPT) (indicators of hepatocellular injury), and bilirubin and gamma-glutamyl transferase (gamma GT) (indicators of liver failure) as well as nitrite (indicator of the induction of nitric oxide synthase; iNOS). Treatment of LPS-rats with BQ-788, but not with BQ-485, attenuated the degree of liver injury and failure, while neither BQ-788 nor BQ-485 affected the acute renal failure or the induction of iNOS caused by endotoxin. 5. Endotoxaemia also caused (within 15 min) an acute metabolic acidosis (falls in pH, HCO3-and base excess) which was compensated by hyperventilation (fall in PaCO2). Treatment of LPS-rats with BQ-788 or BQ-485 did not affect the metabolic acidosis caused by LPS. 6. Thus, the selective ETB receptor antagonist BQ-788 attenuated (i) the delayed hypotension, (ii) the vascular hyporeactivity to NA as well as (iii) the degree of hepatocellular injury and dysfunction caused by endotoxin in the anaesthetized rat. In contrast, the selective ETA receptor antagonist did neither attenuate the circulatory failure nor the liver or rena

Topics: Alanine Transaminase; Analysis of Variance; Animals; Aspartate Aminotransferases; Azepines; Blood Pressure; Creatinine; Endotoxemia; Escherichia coli; Heart Rate; Hypotension; Lipopolysaccharides; Male; Nitric Oxide; Oligopeptides; Piperidines; Rats; Rats, Wistar; Shock, Septic; Urea

(S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pip eridin-3- yl]ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane chloride (SR140333) is a new non-peptide antagonist of tachykinin NK1 receptors. SR140333 potently, selectively and competitively inhibited substance P binding to NK1 receptors from various animal species, including humans. In vitro, it was a potent antagonist in functional assays for NK1 receptors such as [Sar9,Met(O2)11]substance P-induced endothelium-dependent relaxation of rabbit pulmonary artery and contraction of guinea-pig ileum. Up to 1 microM, it had no effect in bioassays for NK2 ([beta Ala8]neurokinin A-induced contraction of endothelium-deprived rabbit pulmonary artery) and NK3 ([MePhe7]neurokinin B-induced contraction of rat portal vein) receptors. The antagonism exerted by SR140333 toward NK1 receptors was apparently non-competitive, with pD2' values (antagonism potency evaluated by the negative logarithm of the molar concentration of antagonist that produces a 50% reduction of the maximal response to the agonist) between 9.65 and 10.16 in the different assays. SR140333 also blocked in vitro [Sar9,Met(O2)11]substance P-induced release of acetylcholine from rat striatum. In vivo, SR140333 exerted highly potent antagonism toward [Sar9,Met(O2)11]substance P-induced hypotension in dogs (ED50 = 3 micrograms/kg i.v.), bronchoconstriction in guinea-pig (ED50 = 42 micrograms/kg i.v.) and plasma extravasation in rats (ED50 = 7 micrograms/kg i.v.). Finally, it also blocked the activation of rat thalamic neurons after nociceptive stimulation (ED50 = 0.2 micrograms/kg i.v.).

Topics: Animals; Brain; Bronchoconstriction; Capillary Permeability; Cell Line; Dogs; Endothelium, Vascular; Guinea Pigs; Humans; Hypotension; Male; Muscle Relaxation; Muscle, Smooth; Neurokinin-1 Receptor Antagonists; Neurons; Piperidines; Quinuclidines; Rabbits; Rats; Rats, Sprague-Dawley; Receptors, Neurokinin-1; Substance P; Tumor Cells, Cultured

p-Dimethoxyaryl analogs of certain potent catechol-derived dopaminergic agonists show dopaminergic properties for which no structure-activity relationship has yet been defined. (S)-3-(3-Hydroxyphenyl)-N-n-propylpiperidine (1, S-"3-PPP") is a dopaminergic autoreceptor agonist, and at high doses it also exhibits postsynaptic antagonism. (R)-1 is a postsynaptic agonist. In a continuation of studies of effects of the p-dimethoxy moiety at dopamine receptors, synthesis and resolution of the 2,5-dimethoxy analog 3 of 3-PPP was undertaken. The two enantiomers and the racemic modification showed cardiovascular effects consistent with actions at DA-2 receptors. The potency of all three compounds was much lower than that of 3-PPP, although they displayed approximately the same duration of action. Absolute configuration does not seem to be a major determinant of these compounds' ability to interact with DA-2 receptors.

Topics: Animals; Bradycardia; Dopamine Agents; Hypotension; Piperidines; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship

E5880 (1-ethyl-2-[N-(2-methoxy)benzoyl-N-[(2R)-2-methoxy-3-(4- octadecylcarbamoyloxy) piperidinocarbonyloxypropyloxy] carbonyl]aminomethylpyridinium chloride, CAS 128420-61-1) is a novel analog-type antagonist of platelet activating factor (PAF). This paper describes the in vitro PAF antagonistic activity of E5880 and its in vivo effect in various experimentally induced shock models. Inhibition by E5880 of [3H]platelet activating factor (PAF) binding to human platelet PAF receptor was extremely potent; its IC50 value was 0.27 nmol/l, so that it was about 5 times more potent than PAF itself. Its IC50 value in inhibition of washed human platelet aggregation induced by PAF was 0.66 nmol/l. Intravenous treatment with E5880 dose-dependently reversed PAF-induced hypotension in rats and protected mice from lethality caused by PAF. Lipopolysaccharide (LPS)-induced hypotension in rats was inhibited by both pre- and post-treatment with E5880. It was also confirmed that blood PAF level, measured by the GC-NICI-MS method, was increased after LPS challenge in this model. Furthermore, E5880 was extremely effective in preventing passive anaphylactic lethality in mice. Blood PAF level in this model was also increased immediately after antigen challenge, and this was coincident with the time at which signs of shock became apparent. These findings support the concept that PAF is an important mediator in the development of LPS-induced shock and anaphylactic shock, and suggest that E5880, a novel and potent PAF antagonist, may be effective in clinical treatment for shock states.

Topics: Animals; Gas Chromatography-Mass Spectrometry; Hypotension; Lipopolysaccharides; Mice; Mice, Inbred ICR; Passive Cutaneous Anaphylaxis; Piperidines; Platelet Activating Factor; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Pyridinium Compounds; Rats; Rats, Inbred F344; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Shock

The effects of intravenous infusions of paroxetine, a novel inhibitor of 5-hydroxytryptamine (5HT) uptake, and of the tricyclic antidepressant, amitriptyline, on the cardiovascular system have been compared in the conscious rabbit and in the anaesthetised cat. As judged by the dose required to produce changes in ECG waveform (including PR and QTc intervals) and disorders of heart rhythm, paroxetine was less cardiotoxic than amitriptyline in both species. Thus, paroxetine has the advantage over amitriptyline of being less toxic to the cardiovascular system which could constitute a considerable advantage in clinical use particularly as other work has shown it to be more potent than amitriptyline in tests for antidepressant activity.

Topics: Amitriptyline; Animals; Antidepressive Agents; Cats; Drug Evaluation, Preclinical; Electrocardiography; Female; Heart Conduction System; Hypotension; Infusions, Parenteral; Male; Myocardial Contraction; Paroxetine; Piperidines; Rabbits; Seizures; Serotonin Antagonists; Tachycardia

The hypotension and bradycardia observed after intravenous injection of dextran sulfate in rabbits was prevented by prior depletion of circulating platelets, but was not prevented by depletion of the third component of complement or Hageman factor. Dextran sulfate injection caused immediate thrombocytopenia with temporary localization of platelets within lungs. Morphological analysis revealed platelet aggregates in lung capillaries. The platelets had changed shape and were in the process of degranulating. Serotonin and histamine levels in blood increased approximately 5-fold and 7-fold, respectively, after dextran sulfate injection. The cardiovascular events following dextran sulfate injection were mimicked by intravenous serotonin but not by intravenous histamine injection, although a combination of serotonin and histamine reproduced the pattern of blood pressure changes better than did either agent alone. Quantification of platelets trapped in lung revealed that the potential release of serotonin from trapped platelets could account for the rise in plasma serotonin concentration and the hemodynamic changes observed. Both the dextran sulfate-induced cardiovascular effects and serotonin-induced hypotension were markedly diminished by cutting vagus and depressor nerves, and were virtually abolished by carotid ligation in addition to nerve section. These results support the concept that platelet activation within rabbit lungs may cause hypotension via serotonin-induced chemoreflexes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Autonomic Nervous System; Blood Platelets; Bradycardia; Chemoreceptor Cells; Cimetidine; Complement C3; Dextran Sulfate; Dextrans; Factor XII; Histamine; Histamine Release; Hypotension; Injections, Intravenous; Ketanserin; Leukocyte Count; Lung; Male; Methysergide; Piperidines; Rabbits; Serotonin

The most potent synthetic reversible thrombin inhibitor described so far, N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide (Ki = 6 nmol/l), was studied with respect to its pharmacodynamics and pharmacokinetics in mice, rats and rabbits. In mice the LD50 was 54 mg/kg i.v. and greater than 800 mg/kg p.o. Prolongation of bleeding time in mice and reduction of mean arterial blood pressure in rats were seen only at doses above the antithrombotically effective doses. After i.v. injection in rabbits the plasma half-life was estimated to be about 9 min. Subcutaneous injection resulted in measurable inhibitor plasma levels for 4 h. Administration of high does into the duodenum did not give antithrombotically effective plasma levels. The ligature of the functional and nutritive hepatic vessels prolonged the half-life of the thrombin inhibitor, whereas renal excretion seems to be of minor importance. A dose-dependent antithrombotic effect was shown in venous stasis-induced thrombosis in rabbits.

Topics: Animals; Blood Coagulation Disorders; Dipeptides; Hypotension; Kinetics; Lethal Dose 50; Liver; Mice; Piperidines; Rabbits; Rats; Rats, Inbred Strains; Thrombin; Thrombosis

Central hypotension is induced by erythro-1-(1-[2-(1,4 - benzodioxan - 2 - yl) - 20H - ET] - 4 - piperidyl) - 2 - benzimidazolinone (R28935), as evidenced by local injections into the cisterna magna of anaesthetized dogs. This hypotensive effect is not inhibited by piperoxan, 100 mug/kg s.o. R28935, contrary to clonidine or norepinephrine, does not provoke vasoconstriction in the perfused isolated artery of the rabbit ear. Very low doses of R28935 antagonize vasoconstriction induced by KC1-depolarization. The centrally-induced hypotension is not due to alpha-adrenergic stimulation.

Topics: Adrenergic alpha-Agonists; Animals; Arteries; Benzimidazoles; Blood Pressure; Clonidine; Depression, Chemical; Dioxanes; Dogs; Ear; Hypotension; Norepinephrine; Piperidines; Rabbits; Regional Blood Flow

Topics: Adrenergic alpha-Agonists; Adult; Aged; Arteriosclerosis; Benzamides; Blood Pressure; Female; Fingers; Heart Rate; Humans; Hypotension; Indoles; Injections, Intravenous; Intermittent Claudication; Male; Middle Aged; Piperidines; Pulse; Radioisotopes; Raynaud Disease; Regional Blood Flow; Skin; Time Factors; Toes; Xenon

Topics: Adult; Aged; Androstanes; Humans; Hypotension; Intubation, Intratracheal; Lung; Middle Aged; Neuromuscular Nondepolarizing Agents; Piperidines; Pressure; Toxiferine; Tubocurarine

Topics: Analgesics; Animals; Antitussive Agents; Body Weight; Cardiovascular System; Constriction; Digestive System; Drug Synergism; Drug Tolerance; Humans; Hypotension; Male; Meperidine; Methods; Mice; Morphine; Nalorphine; Piperidines; Pupil; Rats; Respiration; Substance-Related Disorders; Thiopental

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Bradycardia; Droperidol; Fentanyl; Hypotension; Mice; Morphine; Mortality; Nalorphine; Pharmacology; Piperidines; Research; Toxicology

When chlorothiazide is given to hypertensive patients who are receiving pempidine a rise in plasma pempidine concentration occurs and this is proportionately greater than the additional fall in blood pressure. After pempidine has been added to human whole blood in vitro or in vivo the ratio of the pempidine concentration in the red cells to that in the plasma falls in the course of 1 hr from an initial value greater than 2 to about 1.2. If chlorothiazide is present also, however, the ratio remains constant at 0.7. Changes in the plasma pempidine concentration in vivo probably result from the binding of pempidine to plasma protein in the presence of chlorothiazide. This has been observed in vitro by a dialysis technique.

Topics: Antihypertensive Agents; Blood Pressure; Body Fluids; Chlorothiazide; Erythrocytes; Humans; Hypertension; Hypotension; Male; Pempidine; Piperidines

Topics: Antihypertensive Agents; Humans; Hypotension; Pempidine; Piperidines

Topics: Alkaloids; Azepines; Heterocyclic Compounds, Bridged-Ring; Humans; Hypotension; Lactones; Piperidines

Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypotension; Piperidines; Pyridines